| 1. |
- El-Aarag, Bishoy, et al.
(author)
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Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis
- 2019
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In: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 24:8
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Journal article (peer-reviewed)abstract
- Melittin (MEL) is a 26-amino acid peptide with numerous biological activities. Paraquat (PQ) is one of the most widely used herbicides, although it is extremely toxic to humans. To date, PQ poisoning has no effective treatment, and therefore the current study aimed to assess for the first time the possible effects of MEL on PQ-induced lung injuries in mice. Mice received a single intraperitoneal (IP) injection of PQ (30 mg/kg), followed by IP treatment with MEL (0.1 and 0.5 mg/kg) twice per week for four consecutive weeks. Histological alterations, oxidative stress, and apoptosis in the lungs were studied. Hematoxylin and eosin (H&E) staining indicated that MEL markedly reduced lung injuries induced by PQ. Furthermore, treatment with MEL increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, and decreased malonaldehyde (MDA) and nitric oxide (NO) levels in lung tissue homogenates. Moreover, immunohistochemical staining showed that B-cell lymphoma-2 (Bcl-2) and survivin expressions were upregulated after MEL treatment, while Ki-67 expression was downregulated. The high dose of MEL was more effective than the low dose in all experiments. In summary, MEL efficiently reduced PQ-induced lung injuries in mice. Specific pharmacological examinations are required to determine the effectiveness of MEL in cases of human PQ poisoning.
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| 2. |
- Shahzad, Danish, et al.
(author)
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Novel C-2 Symmetric Molecules as -Glucosidase and -Amylase Inhibitors : Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
- 2019
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In: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:8
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Journal article (peer-reviewed)abstract
- A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a-5h, have been synthesized, characterized by H-1-NMR and C-13-NMR, and evaluated for their in vitro -glucosidase and -amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both -glucosidase and -amylase. The IC50 of 5g against -glucosidase was 0.35917 +/- 0.0189 mu M (standard acarbose IC50 = 6.109 +/- 0.329 mu M), and the IC50 value of 5g against -amylase was 0.4379 +/- 0.0423 mu M (standard acarbose IC50 = 33.178 +/- 2.392 mu M). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of -glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 angstrom, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results
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| 3. |
- Amir, Mohd., et al.
(author)
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Investigating architecture and structure-function relationships in cold shock DNA-binding domain family using structural genomics-based approach
- 2019
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In: International Journal of Biological Macromolecules. - : ELSEVIER SCIENCE BV. - 0141-8130 .- 1879-0003. ; 133, s. 484-494
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Journal article (peer-reviewed)abstract
- Oligonucleotide/oligosaccharide-binding fold (OB-fold) plays a major role in the regulation of central dogma of life via binding though DNA and RNA. The OB-fold domains are diverse in nature and present in large number of proteins with verities of molecular functions. Here, we have investigated the distribution of sequence, structure and repeats of cold shock DNA-binding proteins (CSDB), a member of OB-fold, in all three kingdoms to establish functional relationships. The CSDB is consists of 30 domains with a major contribution of S1 (>110,601 sequences), S12 (>23,760 sequences), S17 (>14,833 sequences) and S28e (>1615 sequence) domains. These domains are largely found in bacteria (70-90%). The number of S1 domain repeats in eukaryota varies from 1 to 15 and are well-correlated with the protein size. The molecular function analysis suggests that a large number of repeats in the S1 domain are involved in diverse molecular functions in bacteria and eukaryotes. In-depth structure analysis of Si, S12, S17 and S28e domain-containing proteins of the OB-fold family provides a reasonable basis to understand the relationship of size and number of repeats with the corresponding molecular functions.
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| 4. |
- Aneja, Babita, et al.
(author)
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Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis
- 2019
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 163, s. 840-852
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Journal article (peer-reviewed)abstract
- Microtubule affinity-regulating kinase 4 (MARK4) is a potential drug target as the same is found to be over expressed in several types of cancers. In search of effective MARK4 inhibitors, we have synthesized and characterized Isatin-triazole hydrazones (9a-i) and evaluated their inhibitory potential. Of all the compounds, 9g showed better binding affinity and enzyme inhibition potential in sub micromolar range. Human serum albumin (HSA) binding assay suggested an easy transportation of 9g in blood stream due to its binding affinity. In vitro anticancer studies performed on MCF-7, MDA-MB-435s and HepG2 cells using 9g showed inhibition of cell proliferation and cell migration. Further, 9g induces apoptosis in these cancerous cells, with IC50 values of 6.22, 9.94 and 8.14 mu M, respectively. Putatively, 9g seems to cause oxidative stress resulting in apoptosis. Functional assay of 9g with a panel of 26 kinases showed MARK4 specific profile. In conclusion, 9g seems to possess an effective inhibitory potential towards MARK4 adding an additional repertoire to anticancer therapeutics.
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| 5. |
- Benchoula, Khaled, et al.
(author)
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Optimization of Hyperglycemic Induction in Zebrafish and Evaluation of Its Blood Glucose Level and Metabolite Fingerprint Treated with Psychotria malayana Jack Leaf Extract
- 2019
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In: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:8
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Journal article (peer-reviewed)abstract
- A standard protocol to develop type 1 diabetes in zebrafish is still uncertain due to unpredictable factors. In this study, an optimized protocol was developed and used to evaluate the anti-diabetic activity of Psychotria malayana leaf. The aims of this study were to develop a type 1 diabetic adult zebrafish model and to evaluate the anti-diabetic activity of the plant extract on the developed model. The ability of streptozotocin and alloxan at a different dose to elevate the blood glucose levels in zebrafish was evaluated. While the anti-diabetic activity of P. malayana aqueous extract was evaluated through analysis of blood glucose and LC-MS analysis fingerprinting. The results indicated that a single intraperitoneal injection of 300 mg/kg alloxan was the optimal dose to elevate the fasting blood glucose in zebrafish. Furthermore, the plant extract at 1, 2, and 3 g/kg significantly reduced blood glucose levels in the diabetic zebrafish. In addition, LC-MS-based fingerprinting indicated that 3 g/kg plant extract more effective than other doses. Phytosterols, sugar alcohols, sugar acid, free fatty acids, cyclitols, phenolics, and alkaloid were detected in the extract using GC-MS. In conclusion, P. malayana leaf aqueous extract showed anti-diabetic activity on the developed type 1 diabetic zebrafish model.
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| 6. |
- Hussain, Afzal, et al.
(author)
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Biogenesis of ZnO nanoparticles using Pandanus odorifer leaf extract : anticancer and antimicrobial activities
- 2019
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In: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 9:27, s. 15357-15369
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Journal article (peer-reviewed)abstract
- The continuously increasing incidence rates of cancer and infectious diseases are open threats to the sustainable survival of animals and humans. In the last two decades, the demands of nanomaterials as modern therapeutic agents have increased. In this study, biogenic zinc oxide nanoparticles (ZnO NPs) were developed from aqueous Pandanus odorifer leaf extract (POLE) and characterized using modern methods and tools, such as electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy and UV-vis spectroscopy, which indicated the formation of very pure, spherical NPs approximately 90 nm in size. The anticancer activity of the ZnO NPs was evaluated by MTT and neutral red uptake (NRU) assays in MCF-7, HepG2 and A-549 cells at different doses (1, 2, 5, 10, 25, 50, 100 g ml(-1)). Moreover, the morphology of the treated cancer cells was examined by phase contrast microscopy. The results suggest that the synthesized ZnO NPs inhibited the growth of the cells when applied a concentration from 50-100 g ml(-1). Moreover, the biogenic ZnO NPs were analysed as an antimicrobial agent against pathogenic bacteria. The highest antibacterial activity was observed against Gram-positive Bacillus subtilis (26 nm) and Gram-negative Escherichia coli (24 mm) at 50 g per well. Complete bacterial growth (100%) vanished 100% upon treatment with ZnO NPs at 85 g ml(-1). Overall, POLE mediated derived biogenic ZnO NPs could serve as a significant anticancer and antimicrobial agent and be used in the development of novel drugs and skin care products.
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| 7. |
- Murugesu, Suganya, et al.
(author)
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Toxicity study on Clinacanthus nutans leaf hexane fraction using Danio rerio embryos
- 2019
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In: Toxicology reports. - : ELSEVIER. - 2214-7500. ; 6, s. 1148-1154
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Journal article (peer-reviewed)abstract
- Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows nontoxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 mu g/ml, 31.25 mu g/ml, 62.5 mu g/ml, 125 mu g/ml, 250 mu g/ml and 500 mu g/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 mu g/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.
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| 8. |
- Ujan, Rabail, et al.
(author)
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Drug-1,3,4-Thiadiazole Conjugates as Novel Mixed-Type Inhibitors of Acetylcholinesterase : Synthesis, Molecular Docking, Pharmacokinetics, and ADMET Evaluation
- 2019
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In: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:5
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Journal article (peer-reviewed)abstract
- A small library of new drug-1,3,4-thiazidazole hybrid compounds (3a-3i) was synthesized, characterized, and assessed for their acetyl cholinesterase enzyme (AChE) inhibitory and free radical scavenging activities. The newly synthesized derivatives showed promising activities against AChE, especially compound 3b (IC50 18.1 +/- 0.9 nM), which was the most promising molecule in the series, and was substantially more active than the reference drug (neostigmine methyl sulfate; IC50 2186.5 +/- 98.0 nM). Kinetic studies were performed to elucidate the mode of inhibition of the enzyme, and the compounds showed mixed-type mechanisms for inhibiting AChE. The Ki of 3b (0.0031 mu M) indicates that it can be very effective, even at low concentrations. Compounds 3a-3i all complied with Lipinski's Rule of Five, and showed high drug-likeness scores. The pharmacokinetic parameters revealed notable lead-like properties with insignificant liver and skin-penetrating effects. The structure-activity relationship (SAR) analysis indicated pi-pi interactions with key amino acid residues related to Tyr124, Trp286, and Tyr341.
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| 9. |
- Zahra, Maram Hussein, et al.
(author)
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Alpinia zerumbet (Pers.) : Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities
- 2019
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In: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 24:13
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Journal article (peer-reviewed)abstract
- Background/Aim: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers. Methods: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model. Results: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, H-1-NMR and C-13-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 mu g/mL, respectively. Conclusion: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.
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