| 1. |
- Thanh Le, Thanh, et al.
(författare)
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Diarylether-Amino Acid Conjugates as New Class of Anticancer Agents
- 2023
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Ingår i: CHEMISTRYSELECT. - : Wiley. - 2365-6549. ; 8:28
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Tidskriftsartikel (refereegranskat)abstract
- Diarylether (DE) is a privileged structure found in both natural products and synthetic compounds including small molecule drugs. We present the synthesis of a series of 13 new DE-amino acid conjugates which were screened for cancer cells antiproliferation activity. Structure-activity relationship suggests ester and phenyl groups in DE-Phe-OEt 4 c are important for the activity. Compound 4 c inhibited strongly MCF-7 3D tumor sphere formation and have favourable calculated physical chemical properties according to Lipinski's rule of 5. Docking study suggests estrogen receptor and/ or 3a-HSD type 3 protein could be the target(s) for anticancer activity of this class of compounds.
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| 2. |
- Chu, Dinh-Toi, et al.
(författare)
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An update on obesity : Mental consequences and psychological interventions
- 2019
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Ingår i: Diabetes & Metabolic syndrome. - : Elsevier. - 1871-4021 .- 1878-0334. ; 13:1, s. 155-160
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Forskningsöversikt (refereegranskat)abstract
- Besides physical consequences, obesity has negative psychological effects, thereby lowering human life quality. Major psychological consequences of this disorder includes depression, impaired body image, low self-esteem, eating disorders, stress and poor quality of life, which are correlated with age and gender. Physical interventions, mainly diet control and energy balance, have been widely applied to treat obesity; and some psychological interventions including behavioral therapy, cognitive behavioral therapy and hypnotherapy have showed some effects on obesity treatment. Other psychological therapies, such as relaxation and psychodynamic therapies, are paid less attention. This review aims to update scientific evidence regarding the mental consequences and psychological interventions for obesity. (c) 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.
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| 3. |
- Pham, Em Canh, et al.
(författare)
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N,2,6-Trisubstituted 1H-benzimidazole derivatives as a new scaffold of antimicrobial and anticancer agents : design, synthesis, in vitro evaluation, and in silico studies
- 2023
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 13:1, s. 399-420
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Tidskriftsartikel (refereegranskat)abstract
- Compounds containing benzimidazole moiety occupy privileged chemical space for discovering new bioactive substances. In continuation of our recent work, 69 benzimidazole derivatives were designed and synthesized with good to excellent yields of 46-99% using efficient synthesis protocol i.e. sodium metabisulfite catalyzed condensation of aromatic aldehydes with o-phenylenediamines to form 2-arylbenzimidazole derivatives followed by N-alkylation by conventional heating or microwave irradiation for diversification. Potent antibacterial compounds against MSSA and MRSA were discovered such as benzimidazole compounds 3k (2-(4-nitrophenyl), N-benzyl), 3l (2-(4-chlorophenyl), N-(4-chlorobenzyl)), 4c (2-(4-chlorophenyl), 6-methyl, N-benzyl), 4g (2-(4-nitrophenyl), 6-methyl, N-benzyl), and 4j (2-(4-nitrophenyl), 6-methyl, N-(4-chlorobenzyl)) with MIC of 4-16 mu g mL(-1). In addition, compound 4c showed good antimicrobial activities (MIC = 16 mu g mL(-1)) against the bacteria strains Escherichia coli and Streptococcus faecalis. Moreover, compounds 3k, 3l, 4c, 4g, and 4j have been found to kill HepG2, MDA-MB-231, MCF7, RMS, and C26 cancer cells with low mu M IC50 (2.39-10.95). These compounds showed comparable drug-like properties as ciprofloxacin, fluconazole, and paclitaxel in computational ADMET profiling. Finally, docking studies were used to assess potential protein targets responsible for their biological activities. Especially, we found that DHFR is a promising target both in silico and in vitro with compound 4c having IC50 of 2.35 mu M.
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| 4. |
- Tai, Thai Duy Phuoc, et al.
(författare)
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Synthesis of new 1,2,3-triazole derivatives from vanillin and beta-naphthol
- 2019
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Ingår i: VIETNAM JOURNAL OF CHEMISTRY. - : WILEY. - 0866-7144 .- 2572-8288. ; 57:1, s. 116-120
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Tidskriftsartikel (refereegranskat)abstract
- We herein report the synthesis of two new 1,2,3-triazole derivatives from vanillin and beta-naphthol. These 1,2,3-triazoles contain the diaryl ether moiety which has been synthesized via SNAr reaction under mild conditions and in excellent yields. Chemical structures of these triazoles were elucidated by spectroscopic analyses (HR-MS, NMR, IR).
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| 5. |
- Tran, Ngoc Hieu, et al.
(författare)
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Genetic profiling of Vietnamese population from large-scale genomic analysis of non-invasive prenatal testing data
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The under-representation of several ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in many populations. Cost and technology limitations remain the challenges in performing large-scale genome sequencing projects in many developing countries, including Vietnam. As one of the most rapidly adopted genetic tests, non-invasive prenatal testing (NIPT) data offers an alternative untapped resource for genetic studies. Here we performed a large-scale genomic analysis of 2683 pregnant Vietnamese women using their NIPT data and identified a comprehensive set of 8,054,515 single-nucleotide polymorphisms, among which 8.2% were new to the Vietnamese population. Our study also revealed 24,487 disease-associated genetic variants and their allele frequency distribution, especially 5 pathogenic variants for prevalent genetic disorders in Vietnam. We also observed major discrepancies in the allele frequency distribution of disease-associated genetic variants between the Vietnamese and other populations, thus highlighting a need for genome-wide association studies dedicated to the Vietnamese population. The resulted database of Vietnamese genetic variants, their allele frequency distribution, and their associated diseases presents a valuable resource for future genetic studies.
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| 6. |
- Ballante, Flavio, et al.
(författare)
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Docking Finds GPCR Ligands in Dark Chemical Matter
- 2020
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 63:2, s. 613-620
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput screening has revealed dark chemical matter, a set of drug-like compounds that has never shown bioactivity despite being extensively assayed. If dark molecules are found active at a therapeutic target, their extraordinary selectivity profiles make excellent starting points for drug development. We explored if ligands of therapeutically relevant G-protein-coupled receptors could be discovered by structure-based virtual screening of the dark chemical matter. Molecular docking screens against crystal structures of the A(2A) adenosine and the D-4 dopamine receptors were carried out, and 53 top-ranked molecules were evaluated experimentally. Two ligands of each receptor were discovered, and the most potent had sub-micromolar affinities. Analysis of bioactivity data showed that the ligands lacked activity at hundreds of off-targets, including several that are associated with adverse effects. Our results demonstrate that virtual screening provides an efficient means to mine the dark chemical space, which could contribute to development of drugs with improved safety profiles.
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| 7. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 8. |
- Bui, Hue T B, et al.
(författare)
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Facile Synthesis of 4-Oxo-4H-quinolizine-2-carboxamide Derivatives
- 2015
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Ingår i: Synthetic Communications. - : Taylor & Francis. - 0039-7911 .- 1532-2432. ; 45:24, s. 2861-2868
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Tidskriftsartikel (refereegranskat)abstract
- A facile synthetic method for the construction of 2-substituted-4-oxo-4H-quinolizine-based core structure has been successfully developed. The synthesis made use of a one-pot Stobbe condensation followed by cyclization starting from the commercially available 2-pyridinecarbaldehyde. The structure of the formed 4-oxo-4H-quinolizine-2-carboxylate was fully confirmed by mass spectra, H-1 NMR and C-13 NMR, correlation spectrography, heteronuclear multiple bond correlation, and heteronuclear single quantum coherence (HSQC) spectra. The ethyl carboxylate moiety was then further functionalized via direct aminolysis by a range of amines to afford the corresponding 4-oxo-4H-quinolizine-2-carboxamides 4a-i in moderate to good yields.
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| 9. |
- Bui, Hue Thi Buu, et al.
(författare)
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Microwave assisted synthesis and cytotoxic activity evaluations of new benzimidazole derivatives
- 2016
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Ingår i: Tetrahedron Letters. - : Elsevier. - 0040-4039 .- 1359-8562. ; 57:8, s. 887-891
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Tidskriftsartikel (refereegranskat)abstract
- Twelve new 2-quinolizinylbenzimidazole and 2-naphthalylbenzimidazole derivatives with various 5- and 6-positioned substituents (aza, H, CH3, Cl, NO2, NH2, OCH3), have been synthesized in moderate to excellent yields via the condensation of 4-oxo-4H-quinolizinecarbaldehyde or naphthalenecarbaldehyde with substituted o-phenylenediamines, o-nitroaniline, and 2,3-pyridinediamine using sodium metabisulfite or sodium hydrosulfite under microwave irradiation. The new benzimidazole derivatives were screened for their cytotoxic activity against the human breast cancer cell line (MCF-7). The results showed on one hand that 2-(substituted quinolizinyl)-1H-benzimidazoles (12b–f) were less active (3–6 fold) than the positive control Tamoxifen (CC50 = 6.52 μM), and on the other hand, among the 2-(substituted naphthalyl)-1H-benzimidazoles series (13a–f), compounds 6,7,8-trimethoxy-3-(5-chloro-1H-benzo[d]imidazol-2-yl)naphthalen-1-ol (13c) (CC50 = 7.48 μM) and 6,7,8-trimethoxy-3-(5-methoxy-1H-benzo[d]imidazol-2-yl)naphthalen-1-ol (13f) (CC50 = 6.43 μM) were found to be as active as Tamoxifen.
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| 10. |
- Duoc, Vo Thanh, et al.
(författare)
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Hydrogen gas sensor based on self-heating effect of SnO2/Pt thin film with ultralow power consumption
- 2024
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Ingår i: International journal of hydrogen energy. - : Elsevier. - 0360-3199 .- 1879-3487. ; 61, s. 774-782
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Tidskriftsartikel (refereegranskat)abstract
- Self-heating of sensing elements on gas sensors is an effective solution to avoid using external heaters. In this paper, a self-heated hydrogen gas sensor is presented. The sensor was created using the DC sputtering method, which involved fabricating it on a thermal-insulating Kapton flexible substrate. This process utilized a thin film of SnO2 with thick 50 nm that was modified with nanoclusters of Pt, serving as the sensing material. The SnO2/Pt material film was analyzed for microstructure and composition by SEM, XRD, and XPS analysis. Infrared images show that the self-heating effect is mainly concentrated in the strip of gas-sensitive material. It showed many good performances, such as high sensitivity (able to detect down to 50 ppm of H2), good selectivity (poor response to CO, NH3, H2S, and NO2), the sensor's performance is little changed by environmental humidity, and low power consumption (89 μW at 5V). The sensor is also stable and low-cost, suitable for portable H2 detection devices due to its low generated heat and small size.
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| 11. |
- Duoc, Vo Thanh, et al.
(författare)
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New Design of ZnO Nanorod- and Nanowire-Based NO2 Room-Temperature Sensors Prepared by Hydrothermal Method
- 2019
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Ingår i: Journal of Nanomaterials. - : HINDAWI LTD. - 1687-4110 .- 1687-4129.
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Tidskriftsartikel (refereegranskat)abstract
- Room-temperature gas sensors are attracting attention because of their low power consumption, safe operation, and long-term stability. Herein, ZnO nanorods (NRs) and nanowires (NWs) were on-chip grown via a facile hydrothermal method and used for room-temperature NO2 gas sensor applications. The ZnO NRs were obtained by a one-step hydrothermal process, whereas the NWs were obtained by a two-step hydrothermal process. To obtain ZnO NW sensor, the length of NRs was controlled short enough so that none of the nanorod-nanorod junction was made. Thereafter, the NWs were grown from the tips of no-contact NRs to form nanowire-nanowire junctions. The gas-sensing characteristics of ZnO NRs and NWs were tested against NO2 gas at room temperature for comparison. The gas-sensing characteristics of the sensors were also tested at different applied voltages to evaluate the effect of the self-activated gas-sensing performance. Results show that the diameter of ZnO NRs and NWs is the dominant parameter of their NO2 gas-sensing performance at room temperature. In addition, self-activation by local heating occurred for both sensors, but because the NWs were smaller and sparser than the NRs, local heating thus required a lower applied voltage with maximal response compared with the NRs.
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| 12. |
- Duoc, Vo Thanh, et al.
(författare)
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Room temperature highly toxic NO2 gas sensors based on rootstock/scion nanowires of SnO2/ZnO, ZnO/SnO2, SnO2/SnO2 and, ZnO/ZnO
- 2021
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 348
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Tidskriftsartikel (refereegranskat)abstract
- Grafted structures between SnO2 and ZnO nanowires were realized in a two-step process of growth. First, the rootstocks of SnO2 or ZnO nanowires were synthesized by thermal evaporation technique. Second, a thin Au layer was sputter deposited on the sample and synthesis of nanowire scions of ZnO or SnO2, respectively, on the rootstocks was realized by thermal evaporation technique again. In both growth steps, SnO2 powder or a mixture of ZnO and carbon powders was use as source materials for the synthesis. Different rootstock/scion combinations of SnO2/ZnO, ZnO/SnO2 nanowires (called heterostructures) and ZnO/ZnO, SnO2/SnO2 nanowires (called homostructures) were synthesised. The fabricated grafted nanowires were examined by field-emission scanning electron microscope and their compositions were analyzed by energy dispersive spectroscopy and X-ray diffraction analysis. The test results indicate that this type of nanostructure material is very promising for NO2 gas sensing at ppt level at room temperature. Among the fabricated structures the SnO2/ZnO nanowires showed the best sensing performance with the high sensitivity and fast response and recovery time. We also discussed the gas sensing mechanism of the fabricated sensors based on the band diagram.
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| 13. |
- Kampen, Stefanie, et al.
(författare)
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Structure-Guided Design of G-Protein-Coupled Receptor Polypharmacology
- 2021
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Ingår i: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773. ; 60:33, s. 18022-18030
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Tidskriftsartikel (refereegranskat)abstract
- Many diseases are polygenic and can only be treated efficiently with drugs that modulate multiple targets. However, rational design of compounds with multi-target profiles is rarely pursued because it is considered too difficult, in particular if the drug must enter the central nervous system. Here, a structure-based strategy to identify dual-target ligands of G-protein-coupled receptors is presented. We use this approach to design compounds that both antagonize the A(2A) adenosine receptor and activate the D-2 dopamine receptor, which have excellent potential as antiparkinson drugs. Atomic resolution models of the receptors guided generation of a chemical library with compounds designed to occupy orthosteric and secondary binding pockets in both targets. Structure-based virtual screens identified ten compounds, of which three had affinity for both targets. One of these scaffolds was optimized to nanomolar dual-target activity and showed the predicted pharmacodynamic effect in a rat model of Parkinsonism.
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| 14. |
- Le, Thanh Thanh, et al.
(författare)
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Anticancer Activity of New 1,2,3-Triazole-Amino Acid Conjugates
- 2021
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Ingår i: Molbank. - : MDPI. - 1422-8599. ; 2021:2
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Tidskriftsartikel (refereegranskat)abstract
- A multistep synthesis was developed to prepare new 1,2,3-triazole-amino acid conjugates (6 and 7). These compounds contain the diaryl ether moiety and were synthesized via SNAr reaction under mild condition and in good yield. Their structures were confirmed by spectroscopic analyses (HR-MS, NMR, IR). These compounds showed significant antiproliferative activity (>30%) toward the breast MCF7 and liver HepG2 cancer cells lines at <10 mu M concentration.
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| 15. |
- Luttens, Andreas, et al.
(författare)
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Virtual Fragment Screening for DNA Repair Inhibitors in Vast Chemical Space
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Fragment-based screening can catalyze drug discovery by identifying novel scaffolds, but this approach is limited by the small chemical libraries studied by biophysical experiments and the challenging hit optimization step. In efforts to identify DNA repair inhibitors, we explored the use of structure-based virtual screening to access ultralarge fragment libraries that cover four orders of magnitude larger fractions of chemical space than traditional techniques. A set of 14 million fragments were docked to 8-oxoguanine DNA glycosylase (OGG1), a challenging drug target involved in cancer and inflammation. Of the 29 top-ranked fragments that were experimentally evaluated, four compounds were shown to bind to OGG1 and X-ray crystallography confirmed the predicted binding modes. Docking of readily synthesizable elaborations guided fragment optimization, leading to the discovery of submicromolar OGG1 inhibitors with anti-inflammatory and anti-cancer effects in cell models. Our results demonstrate that fragment-based virtual screening enables efficient exploration of vast chemical libraries.
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| 16. |
- Matricon, Pierre, et al.
(författare)
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Fragment-based design of selective GPCR ligands guided by free energy simulations
- 2021
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Ingår i: Chemical Communications. - : Royal Society of Chemistry. - 1359-7345 .- 1364-548X. ; 57:92, s. 12305-12308
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Tidskriftsartikel (refereegranskat)abstract
- Fragment-based drug discovery relies on successful optimization of weakly binding ligands for affinity and selectivity. Herein, we explored strategies for structure-based evolution of fragments binding to a G protein-coupled receptor. Molecular dynamics simulations combined with rigorous free energy calculations guided synthesis of nanomolar ligands with up to >1000-fold improvements of binding affinity and close to 40-fold subtype selectivity.
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| 17. |
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| 18. |
- Matricon, Pierre, et al.
(författare)
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Structure-based virtual screening discovers potent and selective adenosine A1 receptor antagonists
- 2023
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 257
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Tidskriftsartikel (refereegranskat)abstract
- Development of subtype-selective leads is essential in drug discovery campaigns targeting G protein-coupled receptors (GPCRs). Herein, a structure-based virtual screening approach to rationally design subtype-selective ligands was applied to the A1 and A2A adenosine receptors (A1R and A2AR). Crystal structures of these closely related subtypes revealed a non-conserved subpocket in the binding sites that could be exploited to identify A1R selective ligands. A library of 4.6 million compounds was screened computationally against both receptors using molecular docking and 20 A1R selective ligands were predicted. Of these, seven antagonized the A1R with micromolar activities and several compounds displayed slight selectivity for this subtype. Twenty-seven analogs of two discovered scaffolds were designed, resulting in antagonists with nanomolar potency and up to 76-fold A1R-selectivity. Our results show the potential of structure-based virtual screening to guide discovery and optimization of subtype-selective ligands, which could facilitate the development of safer drugs.
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| 19. |
- Nguyen, Van Thi, et al.
(författare)
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Elucidation of the nematicidal mode of action of grammicin on Caenorhabditis elegans
- 2022
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Ingår i: Pesticide Biochemistry and Physiology. - : Elsevier BV. - 0048-3575 .- 1095-9939. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- Grammicin (Gra) is derived from the endophytic fungus Xylaria grammica EL000614 and shows nematicidal activity against the devastating root-knot nematode Meloidogyne incognita in-vitro, in planta, and in-field experiments. However, the mechanism of the nematicidal action of Gra remains unclear. In this study, Gra exposure to the model genetic organism Caenorhabditis elegans affected its L1, L2/3, L4, and young adult stages. In addition, Gra treatment increased the intracellular reactive oxygen species (ROS) levels of C. elegans and M. incognita. Molecular docking interaction analysis indicated that Gra could bind and interact with GCS-1, GST4, and DAF-16a in order of low binding energy, followed by SOD-3, SKN-1, and DAF-16b. This implies that the anthelmintic action of Gra is related to the oxidative stress response. To validate this mechanism, we examined the expression of the genes involved in the oxidative stress responses following treatment with Gra using transgenic C. elegans strains such as the TJ356 strain zIs356 [daf-16p::daf-16a/b::GFP + rol-6 (su1006)], LD1 ldIs7 [skn-1p::skn-1b/c::GFP + rol-6 (su1006)], LD1171 ldIs3 [gcs-1p::GFP + rol-6 (su1006)], CL2166 dvIs19 [(pAF15) gst-4p::GFP::NLS], and CF1553 strain muIs84 [(pAD76) sod-3p::GFP + rol-6 (su1006)]. Gra treatment caused nuclear translocation of DAF-16/FoxO and enhanced gst-4::GFP expression, but it had no change in sod-3::GFP expression. These results indicate that Gra induces oxidative stress response via phase II detoxification without reduced cellular redox machinery. Gra treatment also inhibited the nuclear localization of SKN-1::GFP in the intestine, which may lead to a condition in which oxidative stress tolerance is insufficient to protect C. elegans by the inactivation of SKN-1, thus inducing nematode lethality. Furthermore, Gra caused the mortality of two mutant strains of C. elegans, CB113 and DA1316, which are resistant to aldicarb and ivermectin, respectively. This indicates that the mode of action of Gra is different from the traditional nematicides currently in use, suggesting that it could help develop novel approaches to control plant-parasitic nematodes.
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| 20. |
- Panel, Nicolas, et al.
(författare)
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Design of Drug Efficacy Guided by Free Energy Simulations of the β2-Adrenoceptor
- 2023
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 62:22
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Tidskriftsartikel (refereegranskat)abstract
- G-protein-coupled receptors (GPCRs) play important roles in physiological processes and are modulated by drugs that either activate or block signaling. Rational design of the pharmacological efficacy profiles of GPCR ligands could enable the development of more efficient drugs, but is challenging even if high-resolution receptor structures are available. We performed molecular dynamics simulations of the β2 adrenergic receptor in active and inactive conformations to assess if binding free energy calculations can predict differences in ligand efficacy for closely related compounds. Previously identified ligands were successfully classified into groups with comparable efficacy profiles based on the calculated shift in ligand affinity upon activation. A series of ligands were then predicted and synthesized, leading to the discovery of partial agonists with nanomolar potencies and novel scaffolds. Our results demonstrate that free energy simulations enable design of ligand efficacy and the same approach can be applied to other GPCR drug targets.
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| 21. |
- Pham, Em Canh, et al.
(författare)
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Synthesis of a Series of Novel 2-Amino-5-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole Derivatives as Potential Anticancer, Antifungal and Antibacterial Agents
- 2022
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Ingår i: Medicinal chemistry. - : Bentham Science Publishers Ltd.. - 1573-4064. ; 18:5, s. 558-573
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many compounds containing a five-membered heterocyclic ring display exceptional chemical properties and versatile biological activities. Objective: The objective of the present study was to prepare the 5-substituted 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole derivatives and evaluate their potential anticancer, antibacterial and antifungal activities. Methods: Twenty-seven derivatives were synthesized by iodine-mediated cyclization of semicarbazones or thiosemicarbazones obtained from condensation of semicarbazide or thiosemicarbazide and aldehydes. The structures were confirmed by H-1-NMR, C-13-NMR and MS spectra. The antibacterial and antifungal activities were evaluated by diffusion method and the anticancer activities were evaluated by MTT assay. Results: Twenty-seven derivatives have been synthesized in moderate to good yields. A number of derivatives exhibited potential antibacterial, antifungal and anticancer activities. Conclusion: Compounds (1b, 1e and 1g) showed antibacterial activity against Streptococcus faecalis, MSSA and MRSA with MC value ranging between 4 to 64 mu g/mL. Compound (2g) showed antifungal activity against Candida albicans (8 mu g/mL) and Aspergillus niger (64 mu g/mL). Compound (lo) exhibited high cytotoxic activity against HepG2 cell line (IC50 value 8.6 mu M) which is comparable to the activity of paclitaxel, and is non-toxic on LLC-PK1 normal cell line. The structure activity relationship and molecular docking study of the synthesized compounds have also been reported.
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| 22. |
- Qin, Liena, et al.
(författare)
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Diversity-Oriented Synthesis of Libraries Based on Benzofuran and 2,3-Dihydrobenzofuran Scaffolds
- 2017
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Ingår i: ACS Combinatorial Science. - : American Chemical Society (ACS). - 2156-8952 .- 2156-8944. ; 19:6, s. 370-376
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Tidskriftsartikel (refereegranskat)abstract
- Benzofuran and 2,3-dihydrobenzofuran scaffolds are core components in a large number of biologically active natural and synthetic compounds including approved drugs. Herein, we report efficient synthetic protocols for preparation of libraries based on 3-carboxy 2-aryl benzofuran and 3-carboxy 2-aryl trans-2,3-dihydrobenzofuran scaffolds using commercially available salicylaldehydes, aryl boronic acids or halides and primary or secondary amines. The building blocks were selected to achieve variation in physicochemical properties and statistical molecular design and subsequent synthesis resulted in 54 lead-like compounds with molecular weights of 299-421 and calculated octanol/water partition coefficients of 1.9-4.7.
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| 23. |
- Sethio, Daniel, et al.
(författare)
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Simulation Reveals the Chameleonic Behavior of Macrocycles
- 2023
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 63:1, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- Conformational analysis is central to the design of bioactive molecules. It is particularly challenging for macrocycles due to noncovalent transannular interactions, steric interactions, and ring strain that are often coupled. Herein, we simulated the conformations of five macrocycles designed to express a progression of increasing complexity in environment-dependent intramolecular interactions and verified the results against NMR measurements in chloroform and dimethyl sulfoxide. Molecular dynamics using an explicit solvent model, but not the Monte Carlo method with implicit solvation, handled both solvents correctly. Refinement of conformations at the ab initio level was fundamental to reproducing the experimental observations-standard state-of-the-art molecular mechanics force fields were insufficient. Our simulations correctly predicted the intramolecular interactions between side chains and the macrocycle and revealed an unprecedented solvent-induced conformational switch of the macrocyclic ring. Our results provide a platform for the rational, prospective design of molecular chameleons that adapt to the properties of the environment.
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| 24. |
- Sundin, Charlotta, et al.
(författare)
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Exploring resveratrol dimers as virulence blocking agent : Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming. Current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike. One alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability. We have previously show that the plant natural product (-)-hopeaphenol blocks the type III secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. (-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors. To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter. Using a panel of assays we showed that compounds with a benzofuran core structure i.e. viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.
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| 25. |
- Thu Thao, Bui T., et al.
(författare)
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Enhancement of selective monoaromatic hydrocarbon and syngas products from fast pyrolysis of cassava stalks over Co, Mo promoted Ni catalysts
- 2024
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Ingår i: Journal of the Energy Institute. - 1743-9671. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- Catalytic fast pyrolysis of cassava stalks has been intriguing as a promising, feasible chemical refinery method in terms of waste-to-energy conversion from cassava cultivation. This study aims to determine the synergetic influence of Mo and Co on Ni catalysts (Ni, Ni–Mo, and Ni–Co) prepared via ultrasonic-assisted incipient wetness impregnation method for catalytic pyrolysis vapor upgrading. The results indicated that Co and Mo enhance the reducibility of NiO and promote weak-to-medium acidity, thereby enhancing Ni's performance. Mono-Ni favors cracking deoxygenation, whereas oxophilicity promoters particularly enhance the oxygen absorbability efficiency to selective deoxygenated production. A fine Ni dispersion on CoNi/SiO2 catalyst was observed to positively affect the production of monoaromatic hydrocarbons (46.10 %), in contrast to those without promoters (21.63 %). This is attributed to an optimal Ni-metallic distribution with a small crystal size of 7.01 nm and a high surface area of 342.6 m2 g−1, highlighting the effectiveness of the promoter-assisted Ni catalyst. Additionally, a high yield of H2 (66.9 %) in non-condensable gas was recorded at 550 °C. The study suggests that a simplified approach to developing Ni-based catalysts could enhance the eco-friendliness of commercial catalysts, thereby facilitating the scale-up of biomass pyrolysis applications.
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| 26. |
- Vo, Duc Duy, et al.
(författare)
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Building of neomycin-nucleobase-amino acid conjugates for the inhibition of oncogenic miRNAs biogenesis
- 2018
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 16:34, s. 6262-6274
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs are aberrantly expressed in a variety of human cancers, thus being oncogenic. The inhibition of oncogenic miRNAs (defined as the blocking of miRNAs' production or function) would find application in the therapy of different types of cancer in which these miRNAs are implicated. In this work, we describe the design and synthesis of new small-molecule RNA ligands with the aim of inhibiting Dicer-mediated processing of oncogenic miRNAs. One of the synthesized compound (4b) composed of the aminoglycoside neomycin conjugated to an artificial nucleobase and to amino acid histidine is able to selectively decrease miR-372 levels in gastric adenocarcinoma (AGS) cells and to restore the expression of the target LATS2 protein. This activity led to the inhibition of proliferation of these cells. The study of the interactions of 4b with pre-miR-372 allowed for the elucidation of the molecular mechanism of the conjugate, thus leading to new perspectives for the design of future inhibitors.
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| 27. |
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| 28. |
- Vo, Duc Duy, et al.
(författare)
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Total Synthesis of Viniferifuran, Resveratrol-Piceatannol Hybrid, Anigopreissin A and Analogues : Investigation of Demethylation Strategies
- 2016
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley-VCH Verlagsgesellschaft. - 1615-4150 .- 1615-4169. ; 358:24, s. 4085-4092
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Tidskriftsartikel (refereegranskat)abstract
- Resveratrol-based natural products constitute a valuable source of unique compounds with diverse biological activities. In this report we investigate demethylation strategies to minimize formation of cyclized and dimerized products during the synthesis of viniferifuran and analogues. We found that boron trichloride/tetra-n-butylammonium iodide (BCl3/TBAI) is typically more effective than boron tribromide (BBr3). Based on these findings we carried out the first syntheses of dehydro-δ-viniferin, resveratrol-piceatannol hybrid and anigopreissin A. In addition, we have developed a short and efficient route to viniferifuran that was obtained in 13% yield over six steps.
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| 29. |
- Wannberg, Johan, et al.
(författare)
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N-(Heteroaryl)thiophene sulfonamides as angiotensin AT2 receptor ligands
- 2024
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 265
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Tidskriftsartikel (refereegranskat)abstract
- Two series of N-(heteroaryl)thiophene sulfonamides, encompassing either a methylene imidazole group or a tertbutylimidazolylacetyl group in the meta position of the benzene ring, have been synthesized. An AT(2)R selective ligand with a Ki of 42 nM was identified in the first series and in the second series, six AT(2)R selective ligands with significantly improved binding affinities and Ki values of <5 nM were discovered. The binding modes to AT(2)R were explored by docking calculations combined with molecular dynamics simulations. Although some of the high affinity ligands exhibited fair stability in human liver microsomes, comparable to that observed with C21 undergoing clinical trials, most ligands displayed a very low metabolic stability with t(1/2) of less than 10 min in human liver microsomes. The most promising ligand, with an AT(2)R K-i value of 4.9 nM and with intermediate stability in human hepatocytes (t(1/2) = 77 min) caused a concentration-dependent vasorelaxation of pre-contracted mouse aorta.
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