Ecdysteroids, a class of naturally isolated polyhydroxylated sterols, stands at a very good place in the pharmaceutical industry from their medicinal point of views like anti-inflammatory, ...neuroprotective, anti-microbial, anti-diabetic, antioxidant, and anti-tumor effects. Due to their excellent antioxidant and anti-microbial potential, ecdysteroids have extensive use in skin products, especially derma creams. To monitor the best anti-acne phytoecdysteroids, here made use of different computational approaches, by using the rapid, easy, cost-effective and high throughput method to screen and identify ecdysteroids as androgen receptor inhibitors. 3D-QSAR study was carried out on a dataset of ecdysteroids by using comparative molecular field analysis (CoMFA) to determine the factors responsible for the activity of compounds. Statistically a cross-validated (q2) 0.1457 and regression coefficient (r2) 0.9713 indicated the best model. Contour map results showed the influence of steric effect to enhance activity. A molecular docking analysis was done to further find out the binding sites and their anti-acne potential against three crystal structured macromolecules (PDB ID: 2REQ, 2BAC, 4EM0). Docking results were further evaluated by prime MM-GBSA analysis and findings confirmed the accuracy. Toxicity by ADMET assessment was carried out and M2 was found as lead druglike with best anti-acne activity against Propionium acnes GehA lipase bacteria after passing all filters. This research study is novel because it is representing first effort to explore ecdysteroids class for their high therapeutic output as androgen receptor inhibitor by using computational tools and expectedly led to novel scaffold for androgen receptor inhibitor. This is a novel and new approach to investigate the ecdysteroids for first time for their practical applications.
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•3D-QSAR study by using Comparative molecular field analysis (CoMFA) determines the factors responsible for the activity of compounds.•Statistically a cross-validated (q2) 0.1457 and regression coefficient (r2) 0.9713 indicated the best model fit with seven compounds as active ligands.•Screened 7 ligands showed high binding affinity in range of − 7.8 to − 11.8 kcal/mol against receptors (PDB ID: 2REQ, 2BAC) and − 5.5 to − 7.5 kcal/mol against receptor (PDB ID: 4EM0)•2 compounds (M2 & R6) of best binding affinity also fulfill the criteria of Lipinski rule of five.•M2 can serve as an effective lead compound in upcoming exploration for the inhibition of acne.
•Novel thiosemicarbazones synthesized from carbonyl compounds and thiosemicarbazide.•Compounds characterized using UV-Vis and FT-IR spectral techniques.•Demonstrated potent antibacterial activity ...against Bacillus subtilis and Escherichia coli.•Exhibited significant antidiabetic activity, surpassing acarbose in molecular docking.•Promising candidates WS-1 and WS-2 showed lowest binding energies with Alpha-glucosidase.
Thiosemicarbazones and their derivatives were synthesized by reacting carbonyl compounds with thiosemicarbazide, followed by treatment with metal salts. The prepared thisemicarbazones such as (2E)-2-(1,5,7-trichloronaphthalen-2-yl)-methylidene-hydrazine-1-carbothioamide,(2E)-2-(1,5,7-trihydroxynaphthalen-2-yl)-methylidenehydrazine-1-carbothioamide and these were characterized by using diverse spectral techniques, such as UV–Vis and FT-IR. The synthesized compounds were subsequently evaluated for their antibacterial properties against Gram(+) Bacillus subtilis and Gram(-) Escherichia coli, using ciprofloxacin as a reference, as well as for their anti-microbial activities. For the evaluation of anti-diabetic activity, Acarbose served as the reference. Molecular docking results indicated that WS-1 and WS-2 exhibited superior performance against Alpha-glucosidase proteins, evidenced by their lowest binding energies (−8.1 and −8.3 kcal/mol) respectively compared to other ligands. These findings suggest that WS-1 and WS-2 are promising candidates for further research and development by pharmaceutical companies to explore additional biological activities.
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The global economy and public health are seriously at risk because of the COVID-19 outbreak brought on by the SARS-CoV-2. Currently, there is no specific medication available to treat COVID-19 ...patients. A quick method used to find out the treatment of newly developing infectious diseases like SARS COV-2 by drug repurposing. Metronidazole (3-methyl-5-nitroimidazole) is a synthetic, azomycin derivative having strong bacteriocidal and antiparasitic properties. Metronidazole (MTZ) derivatives are commercially broad spectrum containing pertinent antibacterial activity and a reasonable safety profile. MTZ structures were designed using chemdraw professional and subjected to field base and atom base QSAR and displayed good results by identifying 9 compounds as active. Molecular docking was performed with 9 proteins from which highest docking score was ranged from − 6.305 to − 8.044 of MT35 with 7aot as compared to standard drug (Lopinavir, showed docking score − 5.504 with same protein). Docking was further validated by redocking by RMSD score in range of 2 Å. MMGB/SA results showed the negative binding energy values of docked protein–ligand complexes comparable to standard drug and MD stimulation were also performed for the structure flexibility showed 1.00 Å RMSF for three protein at maximum fluctuation. Selected drug (MT35) showed good ADME properties which may need to be synthesized followed by in vitro and in vivo study against SARS-CoV-2.
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This research work offers unrivalled insight into the chemodiversity, antioxidant and enzyme inhibition activities of Allardia tridactylites substantiated by computational analysis. Flowers and ...leaves of A. tridactylites were extracted separately with hexane, chloroform, ethyl acetate and ethanol to prepare four extracts of each part. Highest antioxidant potential for the ATFA and ATFLA fractions was observed in the CUPRAC (cupric ion reducing antioxidant capacity) assay as 115.57 ± 1.16 and 112.79 ± 1.8 mg of trolox equivalents per gram of the extract (mg TE/g extract) respectively, followed by chloroform and ethyl acetate extracts of the leaves and the flowers. In tyrosinase inhibition assay, the ATFE was found most active (28.92 ± 1.42 mg of Kojic acid equivalents per gram of the extract (mg KAE/g extract), while against α-amylase and α-glucosidase, the ATLC (0.63 ± 0.02 mmol of acarbose equivalents per gram of the extract (mmol ACAE/g extract) and ATFH (1.10 ± 0.01 mmol ACAE/g) were the most active respectively. Overall, ATLA and ATFA were rich in phenolics and flavonoids and also exhibited higher antioxidant activities, while in enzyme inhibition assay, the low polar extracts were more active. UHPLC-MS analysis of crude ethanolic extract result in identification of 125 secondary metabolites of various classes. The findings from various multidirectional investigations indicated that this plant held significant importance for the biopharmaceutical industries, as it served as a valuable source for the development of multiple formulations that were effective in targeting major biological enzymes.
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•The current study has provided a multidimensional insight into A. tridactylites.•The chemical composition of A. tridactylites was analyzed by UHPLCMS analysis.•The extracts were subjected to invitro assays to assess their biological properties.•Insilico studies were conducted to further validate the bioactivities of A. tridactylites.
