| 1. |
- Azeem, Muhammad, et al.
(författare)
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Design, synthesis, spectroscopic characterization, in-vitro antibacterial evaluation and in-silico analysis of polycaprolactone containing chitosan-quercetin microspheres
- 2023
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : TAYLOR & FRANCIS INC. - 0739-1102 .- 1538-0254. ; 41:15, s. 7084-7103
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Tidskriftsartikel (refereegranskat)abstract
- Aim of present study was to synthesize a novel chitosan-quercetin (CTS-QT) complex by making a carbodiimide linkage using maleic anhydride as cross-linker and to investigate its enhanced antibacterial and antioxidant activities as compare to pure CTS and QT. Equimolar concentration of QT and maleic anhydride were used to react with 100 mg CTS to form CTS-QT complex. For this purpose, three bacterial strains namely E. Coli, S. Aureus and P. Aeruginosa were used for in-vitro antibacterial analysis (ZOI, MIC, MBC, checker board and time kill assay). Later molecular docking studies were performed on protein structure of E. Coli to assess binding affinity of pure QT and CTS-QT complex. MD simulations with accelerated settings were used to explore the protein-ligand complexs binding interactions and stability. Antioxidant profile was determined by performing DPPH center dot radical scavenging assay, total antioxidant capacity (TAC) and total reducing power (TRP) assays. Delivery mechanism to CTS-QT complex was improved by synthesizing polycaprolactone containing microspheres (CTS-QT-PCL-Levo-Ms) using Levofloxacin as model drug to enhance their antibacterial profile. Resulted microspheres were evaluated by particle size, charge, surface morphology, in-vitro drug release and hemolytic profile and are all were found within limits. Antibacterial assay revealed that CTS-QT-PCL-Levo-Ms showed more than two folds increased bactericidal activity against E. Coli and P. Aeruginosa, while 1.5 folds against S. Aureus. Green colored formation of phosphate molybdate complexes with highest 85 +/- 1.32% TAC confirmed its antioxidant properties. Furthermore, molecular docking and dynamics studies revealed that CTS-QT was embedded nicely within the active pocket of UPPS with binding energy greater than QT with RSMD value of below 1.5. Conclusively, use of maleic acid, in-vitro and in-silico antimicrobial studies confirm the emergence of CTS-QT complex containing microspheres as novel treatment strategy for all types of bacterial infections. Communicated by Ramaswamy H. Sarma
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| 2. |
- Aziz, Mubashir, et al.
(författare)
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A comprehensive computational approach for the identification of structure-based potential pharmacological candidates as selective AKR1B1 and AKR1B10 inhibitors: repurposing of purine alkaloids for the treatment of cancer
- 2023
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : TAYLOR & FRANCIS INC. - 0739-1102 .- 1538-0254. ; 41:16, s. 7892-7912
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Tidskriftsartikel (refereegranskat)abstract
- Significant metabolic pathways have been linked to AKR1B1 and AKR1B10. These enzymes are crucial biological targets in the therapy of colon cancer. In the past several decades, drug repurposing has gained appeal as a time and cost-efficient strategy for providing new indications for existing drugs. The structural properties of the plant-based alkaloidal drugs theobromine and theophylline were examined using density functional theory (DFT) computations, where the B3LYP/SVP method was used to quantify the dipole moment, polarizability, and optimization energy. Optimized structures obtained through DFT studies were docked inside the active pocket of target proteins to evaluate their inhibitory potential. Moreover, molecular dynamic simulation provides significant insight into a dynamic view of molecular interactions. The findings of current revealed theobromine and theophylline as strong AKR1B1 and AKR1B10 inhibitors, respectively. In addition, the anti-cancer potential of theophylline and theobromine was validated by targeting various tumor proteins, i.e. NF-kappa B, cellular tumor antigen P53 and caspase-3 using a molecular docking approach. Theobromine was found to be strongly interacted with NF-kappa B and caspase-3, whereas theophylline potentially inhibited cellular tumor antigen P53. In addition, the ADMET characteristics of theobromine and theophylline were identified, confirming their drug-like capabilities. These results should open the way for further experimental validation and structure-based drug design/repurposing of AKR1B1/AKR1B10 inhibitors for the treatment of colon cancer and associated malignancies. Communicated by Ramaswamy H. Sarma
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| 3. |
- Aziz, Mubashir, et al.
(författare)
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Deep Learning and Structure-Based Virtual Screening for Drug Discovery against NEK7 : A Novel Target for the Treatment of Cancer
- 2022
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 27:13
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Tidskriftsartikel (refereegranskat)abstract
- NIMA-related kinase7 (NEK7) plays a multifunctional role in cell division and NLRP3 inflammasone activation. A typical expression or any mutation in the genetic makeup of NEK7 leads to the development of cancer malignancies and fatal inflammatory disease, i.e., breast cancer, non-small cell lung cancer, gout, rheumatoid arthritis, and liver cirrhosis. Therefore, NEK7 is a promising target for drug development against various cancer malignancies. The combination of drug repurposing and structure-based virtual screening of large libraries of compounds has dramatically improved the development of anticancer drugs. The current study focused on the virtual screening of 1200 benzene sulphonamide derivatives retrieved from the PubChem database by selecting and docking validation of the crystal structure of NEK7 protein (PDB ID: 2WQN). The compounds library was subjected to virtual screening using Auto Dock Vina. The binding energies of screened compounds were compared to standard Dabrafenib. In particular, compound 762 exhibited excellent binding energy of -42.67 kJ/mol, better than Dabrafenib (-33.89 kJ/mol). Selected drug candidates showed a reactive profile that was comparable to standard Dabrafenib. To characterize the stability of protein-ligand complexes, molecular dynamic simulations were performed, providing insight into the molecular interactions. The NEK7-Dabrafenib complex showed stability throughout the simulated trajectory. In addition, binding affinities, pIC50, and ADMET profiles of drug candidates were predicted using deep learning models. Deep learning models predicted the binding affinity of compound 762 best among all derivatives, which supports the findings of virtual screening. These findings suggest that top hits can serve as potential inhibitors of NEK7. Moreover, it is recommended to explore the inhibitory potential of identified hits compounds through in-vitro and in-vivo approaches.
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| 4. |
- Aziz, Mubashir, et al.
(författare)
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Identification of NEK7 inhibitors: structure based virtual screening, molecular docking, density functional theory calculations and molecular dynamics simulations
- 2023
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : TAYLOR & FRANCIS INC. - 0739-1102 .- 1538-0254. ; 41:14, s. 6894-6908
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Tidskriftsartikel (refereegranskat)abstract
- NEK7 is a NIMA related-protein kinase that plays a crucial role in spindle assembly and cell division. Dysregulation of NEK7 protein leads to development and progression of different types of malignancies including colon and breast cancers. Therefore, NEK7 could be considered as an attractive target for anti-cancer drug discovery. However, few efforts have been made for the development of selective inhibitors of NIMA-related kinase but still no FDA approved drug is known to selectively inhibit the NEK7 protein. Dacomitinib and Neratinib are two Enamide derivatives that were approved for treatment against non-small cell lung cancer and breast cancer respectively. Drug repurposing is a time and cost-efficient method for re-evaluating the activities of previously authorized medications. Thus, the present research involves the repurposing of two FDA-approved medications via comprehensive in silico approach including Density functional theory (DFTs) studies which were conducted to determine the electronic properties of the Dacomitinib and Neratinib. Afterward, binding orientation of selected drugs inside NEK7 activation loop was evaluated through molecular docking approach. Selected drugs exhibited potential molecular interactions engaging important amino acid residues of active site. The docking score of Dacomitinib and Neratinib was -30.77 and -26.78 kJ/mol, respectively. The top ranked pose obtained from molecular docking was subjected to Molecular Dynamics (MD) Simulations for investigating the stability of protein-ligand complex. The RMSD pattern revealed the stability of protein-ligand complex throughout simulated trajectory. In conclusion, both drugs displayed inhibitory efficacy against NEK7 protein and provide a prospective therapy option for malignant malignancies linked with NEK7. Communicated by Ramaswamy H. Sarma
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| 5. |
- Aziz, Mubashir, et al.
(författare)
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Identification of potent inhibitors of NEK7 protein using a comprehensive computational approach
- 2022
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Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- NIMA related Kinases (NEK7) plays an important role in spindle assembly and mitotic division of the cell. Over expression of NEK7 leads to the progression of different cancers and associated malignancies. It is becoming the next wave of targets for the development of selective and potent anti-cancerous agents. The current study is the first comprehensive computational approach to identify potent inhibitors of NEK7 protein. For this purpose, previously identified anti-inflammatory compound i.e., Phenylcarbamoylpiperidine-1,2,4-triazole amide derivatives by our own group were selected for their anti-cancer potential via detailed Computational studies. Initially, the density functional theory (DFT) calculations were carried out using Gaussian 09 software which provided information about the compounds stability and reactivity. Furthermore, Autodock suite and Molecular Operating Environment (MOE) softwares were used to dock the ligand database into the active pocket of the NEK7 protein. Both software performances were compared in terms of sampling power and scoring power. During the analysis, Autodock results were found to be more reproducible, implying that this software outperforms the MOE. The majority of the compounds, including M7, and M12 showed excellent binding energies and formed stable protein-ligand complexes with docking scores of - 29.66 kJ/mol and - 31.38 kJ/mol, respectively. The results were validated by molecular dynamics simulation studies where the stability and conformational transformation of the best protein-ligand complex were justified on the basis of RMSD and RMSF trajectory analysis. The drug likeness properties and toxicity profile of all compounds were determined by ADMETlab 2.0. Furthermore, the anticancer potential of the potent compounds were confirmed by cell viability (MTT) assay. This study suggested that selected compounds can be further investigated at molecular level and evaluated for cancer treatment and associated malignancies.
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| 6. |
- Bilal, Muhammad Sajjad, et al.
(författare)
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Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR : Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies
- 2022
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) is an angiogenic factor involved in tumor growth and metastasis. Gremlin has been proposed as a novel therapeutic pathway for the treatment of renal inflammatory diseases, acting via VEGFR 2 receptor. To date, most FDA-approved tyrosine kinase (TK) inhibitors have been reported as dual inhibitors of EGFR and VEGFR 2. The aim of the present study was to find the potent and selective inhibitor of VEGFR 2 specifically for the treatment of renal cancer. Fourteen previously identified anti-inflammatory compounds i.e., 1, 3, 4 oxadiazoles derivatives by our own group were selected for their anti-cancer potential, targeting the tyrosine kinase (TK) domain of VEGFR2 and EGFR. A detailed virtual screening-based study was designed viz density functional theory (DFT) study to find the compounds stability and reactivity, molecular docking for estimating binding affinity, SeeSAR analysis and molecular dynamic simulations to confirm protein ligand complex stability and ADMET properties to find the pharmacokinetic profile of all compounds. The DFT results suggested that among all the derivatives, the 7g, 7j, and 7l were chemically reactive and stable derivatives. The optimized structures obtained from the DFTs were further selected for molecular docking, and the results suggested that 7g, 7j and 7l derivatives as the best inhibitors of VEGFR 2 with binding energy values -46.32, -48.89 and -45.01 kJ/mol. The Estimated inhibition constant (IC50) of hit compound 7j (0.009 mu M) and simulation studies of its complexes confirms its high potency and best inhibitor of VEGFR2. All the derivatives were also docked with EGFR, where they showed weak binding energies and poor interactions, important compound 7g, 7j and 7i exhibited binding energy of -31.01, -33.23 and -34.19 kJ/mol respectively. Furthermore, the anticancer potential of the derivatives was confirmed by cell viability (MTT) assay using breast cancer and cervical cancer cell lines. At the end, the results of ADMET studies confirmed these derivatives as drug like candidates. Conclusively, the current study suggested substituted oxadiazoles as the potential anticancer compounds which exhibited more selectivity towards VEGFR2 in comparison to EGFR. Therefore, the identified lead molecules can be used for the synthesis of more potent derivatives of VEGFR2, along with extensive in vitro and in vivo experiments, that can be used to treat various cancers, especially renal cancers, and to prevent angiogenesis due to aberrant expression of VEGFR2.
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| 7. |
- Ejaz, Syeda Abida, et al.
(författare)
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In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization
- 2022
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- The aberrant expression of aldo keto reductases (AKR1B1 & AKR1B10) has been extensively studied in different types of cancer especially the colon cancer but a very few studies have yet been reported regarding the discovery of inhibitors for the treatment of colon cancer by targeting these isozymes. Therefore, there is a need of selective inhibitors of both targets for the eradication of colon cancer. Currently, the study is focused on the exploration of two quinolone compounds i.e., (S)-(6-Methoxyquinolin-4-yl)[(1S,2R,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinidine) and (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinine) as the potential inhibitors of AKR1B1 and AKR1B10 via detailed in-silico approach. The structural properties including vibrational frequencies, dipole moment, polarizability and the optimization energies were estimated using density functional theory (DFT) calculations; where both compounds were found chemically reactive. After that, the optimized structures were used for the molecular docking studies and here quinidine was found more selective towards AKR1B1 and quinine exhibited maximum inhibition of AKR1B10. The results of molecular docking studies were validated by molecular dynamics simulations which provided the deep insight of stability of protein ligand complex. At the end, the ADMET properties were determined to demonstrate the druglikeness properties of both selected compounds. These findings suggested further exploration of both compounds at molecular level using different in-vivo and in-vitro approaches that will lead to the designing of potential inhibitor of AKR1B1/AKR1B10 for curing colon cancer and related malignancies.
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| 8. |
- Ejaz, Syeda Abida, et al.
(författare)
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New Insight into the Pharmacological Importance of Atropine as the Potential Inhibitor of AKR1B1 via Detailed Computational Investigations: DFTs, ADMET, Molecular Docking, and Molecular Dynamics Studies
- 2023
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Ingår i: Applied Biochemistry and Biotechnology. - : SPRINGER. - 0273-2289 .- 1559-0291. ; 195:8, s. 5136-5157
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine, a pharmaceutically active tropane alkaloid. Using density functional theory (DFT) computations with the B3LYP/SVP functional theory basis set, the most stable geometry of atropine was determined. Additionally, a variety of energetic molecular parameters were calculated, such as the optimized energy, atomic charges, dipole moment, frontier molecular orbital energies, HOMO-LUMO energy gap, molecular electrostatic potential, chemical reactivity descriptors, and molecular polarizability. To determine atropines inhibitory potential, molecular docking was used to analyze ligand interactions within the active pockets of aldo-keto reductase (AKR1B1 and AKR1B10). The results of these studies showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10, which was further validated through molecular dynamic simulations by analyzing root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The results of the molecular docking simulation were supplemented with simulation data, and the ADMET characteristics were also determined to predict the drug likeness of a potential compound. In conclusion, the research suggests that atropine has potential as an inhibitor of AKR1B1 and could be used as a parent compound for the synthesis of more potent leads for the treatment of colon cancer associated with the sudden expression of AKR1B1.
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| 9. |
- Ferreira, Oberdan Oliveira, et al.
(författare)
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Synthesis, In-Silico, In Vitro and DFT Assessments of Substituted Imidazopyridine Derivatives as Potential Antimalarials Targeting Hemoglobin Degradation Pathway
- 2023
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Ingår i: JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY. - : WORLD SCIENTIFIC PUBL CO PTE LTD. - 2737-4165. ; 22:7, s. 795-814
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Tidskriftsartikel (refereegranskat)abstract
- Malaria is a serious illness transmitted through the bite of an infected mosquito, which is caused by a type of parasite called plasmodium and can be fatal if left untreated. Thus, newer antimalarials with unique mode of actions are encouraged. Fused pyridines have been vastly reported for numerous pharmacological activities including but not limited to analgesics, antitubercular, antifungal, antibacterial and antiapoptotic agents. In a current study, a series of substituted Imidazo[1,2-a]pyridine-3-carboxamides (IMPCs) (SM-IMP-01-13) along with some hydrazides (DA-01-DA-02) were synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR), 1H-/13C-NMR (proton/carbon nuclear magnetic resonance), elemental analyses and mass spectra. These synthesized analogies were subjected for in vitro biological activities such as Brine Shrimp lethality (BSL), and assay of ss-hematin formation inhibitions. The BSL assay results suggested that compounds, SM-IMP-09, SM-IMP-05 were found to be less toxic and they also had comparable toxicity as of 5-Flurouracil (control) ((e.g., at 10 mu g/ml: 20% deaths of nauplii). Derivatives SM-IMP-02, and DA-05 inhibited ss-hematin formation: IC50: 1.849 and 0.042 mu M, respectively). Our molecular docking analysis on plasmodial cysteine protease falcipain-2 indicated that compound DA-05 (-9.993 kcal/mol) had highest docking score and it was comparable to standard Chloroquine (-7.673 kcal/mol). The most active molecule, DA-05 was also retained with lower HOMO-LUMO energy gap as 3.36 eV. Further, we have also analyzed MEP, and other global reactivity indexes for all IMPCs using DFT. Finally, our in-silico pharmacokinetic analysis suggested that all compounds were having good% human oral absorption values (approximate to 100%), good Caco-2 cell permeabilities (>1600 nm/s), and non-carcinogenic profiles.
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| 10. |
- Jabeen, Mehreen, et al.
(författare)
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Exploring the Antioxidant and Anti-Inflammatory Potential of Wilckia maritima: In Vitro and In Silico Investigations
- 2023
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Ingår i: Processes. - : MDPI. - 2227-9717. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- This research aimed to assess the anti-inflammatory and antioxidant potential of methanol extract of Wilckia maritima, a plant belonging to the family Brassicaceae, which is enriched with natural antioxidants. Qualitative phytochemical studies showed the presence of numerous compounds including glycosides, phenols, triterpenoids, and GC-MS studies revealed the presence of 35 bioactive components, including n-hexadecanoic acid (26.96%), 9,12,15 octadecatrienoic acid (cis) (25.52%), 3,5 di-hydroxy-6-methyl 2,3-di-hydro-4-pyran 4-one (14.35%), and 3-tertiary butyl-4-hydroxy-anisol (11.68%) as major components, which are thought to be responsible for anti-inflammatory and antioxidant potentials of methanol extract of W. maritima., flavonoids, steroids, tannins, and saponins. The antioxidant potential of the extract was determined by performing various assays, including DPPH free radical scavenging, ferrous reducing, and hydrogen peroxide assays, which showed significant percentage inhibition (83.55 +/- 0.89, 79.40 +/- 1.17, and 81.26 +/- 0.36%, respectively) as compared to ascorbic acid (standard). The extract also exhibited significant anti-inflammatory activity with percentage inhibition 65.66 +/- 0.42% compared to standard ibuprofen, which showed 73.20 +/- 0.21% inhibition. In vivo analysis further confirmed this anti-inflammatory potential of the extract, showing a 75.55 +/- 0.11% reduction in edema at 300 mg/kg as compared with standard diclofenac sodium 70.27 +/- 0.012%. Moreover, in silico investigations revealed that the phytocompounds in W. maritima exhibited excellent antioxidant and anti-inflammatory characteristics, which could provide novel biological molecules for target receptors. Overall, our findings suggest that W. maritima can be utilized as a potential resource of natural compounds with antioxidants and anti-inflammatory potential, with promising therapeutic effect in relieving various ailments related to inflammatory response.
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| 11. |
- Li, Yiran, et al.
(författare)
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Vibration-Regulated Multi-State Long-Lived Emission from Star-Shaped Molecules
- 2022
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773. ; 61:48
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Tidskriftsartikel (refereegranskat)abstract
- How to utilize molecular vibration to tune triplet-involved emissions in multiple states is highly challenging. Here, star-shaped triphenylamine derivatives have been employed as model systems to understand how molecular vibration affects thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) emissions in multiple states. Nonplanar, star-shaped conformations allow molecules to generate appropriate vibrations in the solution state, facilitating vibronic coupling between their T-1 and T-2 states to generate effective TADF. More importantly, a relatively dispersed state can allow the molecules to efficiently vibrate in the solid state, and a crystalline environment further promotes a more efficient TADF. Lastly, by suppressing molecular vibration to inhibit the TADF, ultra-long RTP was observed upon doping these molecules into polymers. These molecules can be used in information encryption and storage as well as bioimaging.
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| 12. |
- Liu, Juanjuan, et al.
(författare)
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Photoinduced Carbonyl Radical Luminescence in Host-Guest Systems
- 2023
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Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 15:50, s. 58888-58896
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Tidskriftsartikel (refereegranskat)abstract
- Developing a free radical emission system in different states, especially in water, is highly challenging and desired. Herein, a host-guest coassembly strategy was used to protect the in situ photoactivated radical emission of carbonyl compounds in solid and aqueous solutions by doping them into a series of small molecules with hydroxyl groups. The intermolecular interactions between host and guest and the electron-donating ability of the hydroxyl group can significantly promote the formation and stabilization of luminescence by carbonyl radicals. Accordingly, the stimuli-responsive property of the free radical system was investigated in detail, and the self-assembled aggregates showed photoactive and thermoresponsive behaviors. In addition, an advanced ammonia compound identification system can be built based on a radical emission system. Our design strategy sheds light on developing free radical systems that can emit in various states, which will greatly broaden the application range of free radicals.
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| 13. |
- Nebbach, Diae, et al.
(författare)
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Designing new donors organic compounds with IDIC core for photovoltaic application
- 2022
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Ingår i: Optik (Stuttgart). - : ELSEVIER GMBH. - 0030-4026 .- 1618-1336. ; 262
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Tidskriftsartikel (refereegranskat)abstract
- To search for high-performance pi-conjugated donor molecules used in organic solar cells with heterojunction, Density Functional Theory (DFT) and TD-DFT using B3LYP/6-31 G(d,p) method were used to design and characterize three donor molecules (A2 - A1 - D - A1 - A2) type derived from IDIC (reference) based on indacinodithiophene. These donor molecules were designed by adding the acceptor groups: 2-methyl benzimidazole forming (D1), 2-methyl benzotriazole forming (D2), 2-1-3 benzothiadiazole forming (D3) to both ends of the reference compound IDIC. Their geometric, optoelectronic properties and quantum chemical parameters were examined. The energy driving force (ΔELUMO), the exciton binding energy (EB), the reorganization energy (RE) and the open-circuit voltage (Voc) were also calculated to give a basic insight into the performance of their cells. Because of their wide and red-shifted absorption, low (EB), low (RE) and high (Voc), the findings showed that these materials can be excellent candidates for photovoltaic applications.
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| 14. |
- Pander, Piotr, et al.
(författare)
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Thermally activated delayed fluorescence in a deep red dinuclear iridium(iii) complex: a hidden mechanism for short luminescence lifetimes
- 2023
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Ingår i: Chemical Science. - : ROYAL SOC CHEMISTRY. - 2041-6520 .- 2041-6539. ; 14:47, s. 13934-13943
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Tidskriftsartikel (refereegranskat)abstract
- The high luminescence efficiency of cyclometallated iridium(III) complexes, including those widely used in OLEDs, is typically attributed solely to the formally spin-forbidden phosphorescence process being facilitated by spin-orbit coupling with the Ir(III) centre. In this work, we provide unequivocal evidence that an additional mechanism can also participate, namely a thermally activated delayed fluorescence (TADF) pathway. TADF is well-established in other materials, including in purely organic compounds, but has never been observed in iridium complexes. Our findings may transform the design of iridium(III) complexes by including an additional, faster fluorescent radiative decay pathway. We discover it here in a new dinuclear complex, 1, of the form [Ir(N<^>C)(2)](2)(mu-L), where N<^>C represents a conventional N<^>C-cyclometallating ligand, and L is a bis-N<^>O-chelating bridging ligand derived from 4,6-bis(2-hydroxyphenyl)-pyrimidine. Complex 1 forms selectively as the rac diastereoisomer upon reaction of [Ir(N<^>C)(2)(mu-Cl)](2) with H2L under mild conditions, with none of the alternative meso isomer being separated. Its structure is confirmed by X-ray diffraction. Complex 1 displays deep-red luminescence in solution or in polystyrene film at room temperature (lambda(em) = 643 nm). Variable-temperature emission spectroscopy uncovers the TADF pathway, involving the thermally activated re-population of S-1 from T-1. At room temperature, TADF reduces the photoluminescence lifetime in film by a factor of around 2, to 1 mu s. The TADF pathway is associated with a small S-1-T-1 energy gap Delta E-ST of approximately 50 meV. Calculations that take into account the splitting of the T-1 sublevels through spin-orbit coupling perfectly reproduce the experimentally observed temperature-dependence of the lifetime over the range 20-300K. A solution-processed OLED comprising 1 doped into the emitting layer at 5 wt% displays red electroluminescence, lambda(EL) = 625 nm, with an EQE of 5.5% and maximum luminance of 6300 cd m(-2).
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| 15. |
- Saeed, Amna, et al.
(författare)
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Discovery of Phenylcarbamoylazinane-1,2,4-Triazole Amides Derivatives as the Potential Inhibitors of Aldo-Keto Reductases (AKR1B1 & AKRB10) : Potential Lead Molecules for Treatment of Colon Cancer
- 2022
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 27:13
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Tidskriftsartikel (refereegranskat)abstract
- Both members of the aldo-keto reductases (AKRs) family, AKR1B1 and AKR1B10, are over-expressed in various type of cancer, making them potential targets for inflammation-mediated cancers such as colon, lung, breast, and prostate cancers. This is the first comprehensive study which focused on the identification of phenylcarbamoylazinane-1, 2,4-triazole amides (7a-o) as the inhibitors of aldo-keto reductases (AKR1B1, AKR1B10) via detailed computational analysis. Firstly, the stability and reactivity of compounds were determined by using the Guassian09 programme in which the density functional theory (DFT) calculations were performed by using the B3LYP/SVP level. Among all the derivatives, the 7d, 7e, 7f, 7h, 7j, 7k, and 7m were found chemically reactive. Then the binding interactions of the optimized compounds within the active pocket of the selected targets were carried out by using molecular docking software: AutoDock tools and Molecular operation environment (MOE) software, and during analysis, the Autodock (academic software) results were found to be reproducible, suggesting this software is best over the MOE (commercial software). The results were found in correlation with the DFT results, suggesting 7d as the best inhibitor of AKR1B1 with the energy value of -49.40 kJ/mol and 7f as the best inhibitor of AKR1B10 with the energy value of -52.84 kJ/mol. The other potent compounds also showed comparable binding energies. The best inhibitors of both targets were validated by the molecular dynamics simulation studies where the root mean square value of <2 along with the other physicochemical properties, hydrogen bond interactions, and binding energies were observed. Furthermore, the anticancer potential of the potent compounds was confirmed by cell viability (MTT) assay. The studied compounds fall into the category of drug-like properties and also supported by physicochemical and pharmacological ADMET properties. It can be suggested that the further synthesis of derivatives of 7d and 7f may lead to the potential drug-like molecules for the treatment of colon cancer associated with the aberrant expression of either AKR1B1 or AKR1B10 and other associated malignancies.
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| 16. |
- Shah, Said Nasir, et al.
(författare)
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Bioactive, antioxidant and antimicrobial properties of chemically fingerprinted essential oils extracted from Eucalyptus globulus: in-vitro and in-silico investigations
- 2023
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Ingår i: Frontiers in Chemistry. - : FRONTIERS MEDIA SA. - 2296-2646. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Innovative approaches are urgently required to treat divestating bacterial diseases in the face of rising bacterial resistance rates. The current investigative work focused on hydro-distilling Tasmanian blue gum (Eucalyptus globulus) to isolate the essential oil, which was then tested for bioactivity, antioxidant capacity, and antibacterial activity using in-vitro and in silico assays. The antioxidant activity was avualated against DPPH and FRAP. With results of 69.63 RSA (%) (mu L/L AAE) at a concentration of 5 mL/L and 51.56 (mu L/L AAE) at concentration of 90 ppm in the 2,20-diphenyl-1-picryl hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays, respectively, the extracted oil indicated considerable antioxidant activity. The extracted oil demonstrated powerful antibacterial activity in in-vitro tests against both Gram-positive and Gram-negative bacterial strains, including Bordetella bronchiseptica (21 mm), Staphylococcus epidermidis (19 mm), and Staphylococcus aureus (19 mm), with significant minimal inhibitory (MIC) and minimum bactericidal (MIB) concentrations. Additionally, GC-MS analysis of the oil from E. globulus identified several low-molecular-weight compounds, including Eucalyptol, gamma-Terpinene, Shisool acetate, 1,3-trans,5-cis-Octatriene, 2,6-Dimethyl-1,3,5,7-octatetraene, E,E, Cyclohexene, 1-methyl-4-(1-methylethylidene), Benzene, 1-methyl-4-(1-methylethenyl), Butanoic acid, 3-methyl-, 3-methylbutyl ester, and 1,3,8-p-Menthatriene. Several other compounds were also identified, including Fenchol, 2-Methyl-trans-3a,4,7,7a-tetrahydroindane, (E,E,E)-2,4,6-Octatriene, 1,2,3,6-Tetrahydrobenzylalcohol, acetate, Alloaromadendrene, Phenol, 2-ethyl-4,5-dimethyl, Phenol, 2-methyl-5-(1-methylethyl)-, p-Cymen-7-ol, 1,5,5-Trimethyl-6-methylene-cyclohexene, 1,3-Cyclohexadiene, 1-methyl-4-(1-methylethyl)-, 2,6-Octadien-1-ol, 3,7-dimethyl-, acetate, (Z), and more. The bioactive potential of Eucalyptus globulus essential oil against 1AJ6 and 1R4U was highlighted by molecular docking analyses, suggesting its utility as a natural source of antioxidant and antibacterial compounds with the potential to replace chemical disinfectants in a variety of applications.
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| 17. |
- Taibi, Mohamed, et al.
(författare)
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Phytochemical characterization and multifaceted bioactivity assessment of essential oil from Ptychotis verticillata Duby: Anti-diabetic, anti-tyrosinase, and anti-inflammatory activity
- 2024
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Ingår i: Heliyon. - : CELL PRESS. - 2405-8440. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to explore the pharmacological properties of the essential oil derived from Ptychotis verticillata Duby (PVEO), a medicinal plant native to Morocco, focusing on its antidiabetic, anti-tyrosinase, and anti-inflammatory effects. Additionally, the study aims to characterize the phytochemical composition of PVEO and evaluate its potential as a natural therapeutic alternative for various health conditions. To achieve this, phytochemical analysis was conducted using gas chromatography-mass spectrometry (GC-MS). Furthermore, in vitro assessments were conducted to investigate PVEO's antidiabetic activity by inhibiting alpha-amylase, xanthine oxidase, and alpha-glucosidase. Tests were also undertaken to evaluate the anti-inflammatory effect of PVEO on RAW 264.7 cells stimulated by lipopolysaccharide (LPS), as well as its efficacy as an antityrosinase agent and its lipoxygenase inhibition activity. The results of the phytochemical analysis revealed that PVEO is rich in terpene compounds, with percentages of 40.35 % gamma-terpinene, 22.40 % carvacrol, and 19.77 % beta-cymene. Moreover, in vitro evaluations demonstrated that PVEO exhibits significant inhibitory activity against alpha-amylase, xanthine oxidase, and alpha-glucosidase, indicating promising antidiabetic, and anti-gout potential. Furthermore, PVEO showed significant anti-tyrosinase activity, with an IC50 of 27.39 +/- 0.44 mu g/mL, and remarkable lipoxygenase inhibition (87.33 +/- 2.6 %), suggesting its candidacy for dermatoprotection. Additionally, PVEO displayed a dose-dependent capacity to attenuate the production of NO and PGE2, two inflammatory mediators implicated in various pathologies, without compromising cellular viability. The findings of this study provide a solid foundation for future research on natural therapies and the development of new drugs, highlighting the therapeutic potential of PVEO in the treatment of gout, diabetes, pigmentation disorders, and inflammation.
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| 18. |
- Tong, Danqing, et al.
(författare)
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Achieving short-wavelength free radical emission by combining small conjugated structure and anti-Kasha emission
- 2023
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Ingår i: Dyes and pigments. - : ELSEVIER SCI LTD. - 0143-7208 .- 1873-3743. ; 219
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Tidskriftsartikel (refereegranskat)abstract
- Since the natural narrow bandgaps of free radicals usually lead to emission in the long-wavelength region, it is still of great challenge to design radical luminescent materials with stable and short-wavelength emission in the ambient environment. In this work, a series of dicarbonyl-substituted organic molecules with small conjugated structures were used to form free radicals with short-wavelength radical emission. These low-conjugated mol-ecules with only one benzene ring showed stable photoinduced free radical emission after doping with poly-methyl methacrylate (PMMA) because the rigid polymer environment could help stabilize the free radicals and limit the non-radiative energy transfer. Moreover, PMMA with electron-withdrawing groups could promote the generation of carbonyl radical cations. The theoretical calculation suggests that the free radical with anti-Kasha emission derived from high energy excited state (D4 or D5) would directly relax to the ground state, combining with the small spin delocalization of the low conjugation free radical, leading to short-wavelength emission. More importantly, such free radical emissions could also respond to external stimulation such as light irradiation or heat treatment. These materials show great potential in lithography information recording and information encryption. This design strategy provides new insights into molecular and functional diversity of free radical materials.
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| 19. |
- Zheng, Wei, et al.
(författare)
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Bright Free-Radical Emission in Ionic Liquids
- 2023
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773.
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Tidskriftsartikel (refereegranskat)abstract
- It is challenging to achieve stable and efficient radical emissions under ambient conditions. Herein, we present a rational design strategy to protect photoinduced carbonyl free radical emission through electrostatic interaction and spin delocalization effects. The host-guest system is constructed from tricarbonyl-substituted benzene molecules and a series of imidazolium ionic liquids as the guest and host, respectively, whereby the carbonyl anion radical emission can be in situ generated under the light irradiation and further stabilized by electrostatic interaction. More importantly, the anion species and the alkyl chain length of imidazolium ionic liquids show a noticeable effect on luminescence efficiency, with the highest radical emission efficiency is as high as 53.3 % after optimizing the imidazole ionic liquids structure, which is about four times higher than the polymer-protected radical system. Theoretical calculations confirm the synergistic effect of strong electrostatic interactions and that the spin delocalization effect significantly stabilizes the radical emission. Moreover, such a radical emission system also could be integrated with a fluorescent dye to induce multi-color or even white light emission with reversible temperature-responsive characteristics. The radical emission system can also be used to detect different amine compounds on the basis of the emission changes and photoactivation time.
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| 20. |
- Zouhri, Aziz, et al.
(författare)
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Ionomic analysis, polyphenols characterization, analgesic, antiinflammatory and antioxidant capacities of Cistus laurifolius leaves : in vitro, in vivo, and in silico investigations
- 2023
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to investigate the chemical and mineral composition, antioxidant, analgesic, and anti-inflammatory effects of the aqueous extract of Cistus laurifolius var. atlanticus Pit. (Cistaceae). Additionally, molecular docking interactions of various ligands with antioxidant protein target urate oxidase (1R4U) and anti-inflammatory protein target cyclooxygenase-2 (3LN1), revealing potential dual activities and highlighting specific residue interactions. The chemical characterization focused at first glance on the mineral composition which showed that C. laurifolius extract is a mineral-rich source of potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), phosphorus (P), and zinc (Zn). We next performed, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, the latter showed various polyphenols in C. laurifolius extract including Gallic acid as the predominant polyphenol. Isoquercetin, Taxifolin and Astragalin were also among the major flavonoids detected. The antioxidant capacity of C. laurifolius leaves was tested using 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1- picrylhydrazyl (DPPH) and reducing power (RP) assays. In vitro analysis of the anti-inflammatory property of C. laurifolius leaves was conducted by the albumin denaturation test and the in vivo was assessed in the sequel by carrageenan-induced paw edema test. The analgesic activity was evaluated in vivo using tail flick, acetic acid-induced contortion, and plantar tests. The findings showed that the leave extract had a powerful antioxidant activity with an IC50 values of 2.92 ± 0.03 µg/mL (DPPH) and 2.59 ± 0.09 µg/mL (in RP test). The studied extract strongly abolished the induced inflammation (82%). Albumin denaturation test recorded an IC50 value of 210 µg/mL. Importantly, the oral administration of C. laurifolius extract considerably reduced the nociceptive effect of acetic acid in rats, showing a significant analgesic effect in a dose-related manner. Altogether, our results showed that C. laurifolius can be a promising source of phytochemicals for drug development potential. © 2023, The Author(s).
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