Novel thiophene Chalcones-Coumarin as acetylcholinesterase inhibitors: Design, synthesis, biological evaluation, molecular docking, ADMET prediction and molecular dynamics simulation

Hasan, Aso Hameed; Murugesan, Sankaranarayanan; Amran, Syazwani Itri; Chander, Subhash; Alanazi, Mohammed M.; Hadda, Taïbi Ben; Shakya, Sonam; Pratama, Mohammad Rizki Fadhil; Das, Basundhara; Biswas, Subhrajit; Jamalis, Joazaizulfazli

doi:10.1016/j.bioorg.2021.105572

Cited by 53 publications

(49 citation statements)

References 80 publications

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“…Chemoinformatics (in silico techniques) was used as an efficient approach in drug discovery with the advantage of saving time, effort, and costs [11][12][13]. This includes molecular docking [14,15], ADMET assessment [15] and MD simulation techniques [14,16].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

et al. 2022

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We report herein, the design and synthesis of thiazolidine-2,4-diones derivatives as new inhibitors for VEGFR-2. The designed members were assessed for their in vitro anticancer activity against four cancer cell lines; A549, Caco-2, HepG-2 and MDA-MB-231. Compound 14a showed the most potent effects against Caco-2, and HepG-2 cell lines (IC50 = of 1.5 and 31.5 μM, respectively). Next, the in vitro VEGFR-2 inhibitory activity, safety profiles and selectivity indices were examined for all the synthesized members against the normal Vero cell line. Compound 14a (the safest member against Caco-2 cell line) was further investigated for its ability to inhibit Caco-2 cells migration and healing. Moreover, the apoptotic induction of compound 14a against Caco-2 cell line was investigated by assessing against four apoptotic genes (Bcl2, Bcl-xl, TGF, and Survivin). The results revealed that compound 14a can exert apoptosis through significant reduction of Bcl2, Survivin, and TGF gene expression levels. Finally, deep computational studies including molecular docking, ADMET, toxicity studies, and MD simulation were carried out. Also, the DFT calculations were performed and discussed, and the results confirmed the inhibitory reactivity of 14a against VEGFR-2. Compound 14a is expected to be used as a potential lead in the development of new VEGFR-2 inhibitors with increased potency.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

et al. 2022

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“…In-silico prediction of ADME properties of the selected phytochemicals was carried out using SwissADME online server [120] , while toxicity was predicted using the Organ toxicity and Genomic toxicity model from admetSAR 2.0 [121] as reported in literature [122] . The organ toxicity is classified under the category: Drug-induced liver injury, Human ether-a-go-go-related gene (hERG) inhibition, acute toxicity, Eye injury and Eye corrosion.…”

Section: Methodsmentioning

confidence: 99%

Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies

Hussen¹,

Hasan²,

Jamalis³

et al. 2022

Computational Toxicology

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“…According to the reported procedures, as described in the literature [ 34 ], prediction of drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of the synthesized compounds was carried out utilizing online servers such as SwissADME, ProTox-II, and pkCSM.…”

Section: Methodsmentioning

confidence: 99%

One-pot synthesis, molecular docking, ADMET, and DFT studies of novel pyrazolines as promising SARS-CoV-2 main protease inhibitors

et al. 2022

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Pyrazoline and its derivatives have numerous prominent pharmacological effects. Focusing on its anti-viral property, we have designed and synthesized three novel pyrazoline derivatives ( A1–A3 ) through one-pot three components and characterized them using different spectroscopic techniques (FT-IR, 1 H NMR, 13 C NMR, and UV). These compounds were evaluated against SARS-CoV-2 main protease utilizing in-silico molecular docking studies. The docking results displayed good inhibitory activity of the synthesized compounds. Among them, compound A2 was the most active against targeted protein. The drug-likeness and ADMET properties were predicted to have varied profiles but could still be developed, especially A2 . DFT/TD-DFT calculations through B3LYP/6-311G++ level of theory were applied to provide comparable theoretical data along with MEP map and electronic energy gap of HOMO → LUMO. Supplementary Information The online version contains supplementary material available at 10.1007/s11164-022-04831-5.

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Novel thiophene Chalcones-Coumarin as acetylcholinesterase inhibitors: Design, synthesis, biological evaluation, molecular docking, ADMET prediction and molecular dynamics simulation

Cited by 53 publications

References 80 publications

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies

One-pot synthesis, molecular docking, ADMET, and DFT studies of novel pyrazolines as promising SARS-CoV-2 main protease inhibitors

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