New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2021, Номер 37(1), С. 403 - 416

Опубликована: Дек. 27, 2021

A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features VEGFR-2 inhibitors. Cytotoxic activities evaluated for all against two human cancer cell lines, MCF-7 HepG2. Also, effect most cytotoxic on protein concentration was assessed by ELISA. Compounds

Язык: Английский

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Synthesis, Characterization, in silico DFT, Molecular docking, ADMET Profiling Studies and Toxicity Predictions of Ag(I) Complex Derived from 4‐Aminoacetophenone

ChemistrySelect, Год журнала: 2024, Номер 9(4)

Опубликована: Янв. 22, 2024

Abstract The reaction of the synthesized (E)‐1‐(4‐((2,4‐dihydroxy‐6‐methylphenyl)diazenyl)phenyl)ethan‐1‐one, (DMPDE) ligand with Ag(I) ion at room temperature resulted in formation complex; [Ag(DMPDE)(H 2 O) ]. 1 H NMR, 13 C FTIR, UV‐Vis, mass spectra, elemental analyses, thermal analysis (TGA/DTA), and molar conductance measurements were done to elucidate structure synthetic compounds. results revealed an interesting geometrical variation; tetrahedral for complex. FT‐IR spectra demonstrated that under investigation behaves as a bidentate (N,O) through nitrogen atom azo group which is farthest acetophenone moiety oxygen phenolic benzene forms stable five‐membered chelating ring. electronic structure, molecular electrostatic potential (MEP) quantum chemical calculations newly compounds are investigated theoretically DFT/B3LYP level theory. Additionally, complex screened against growth pathogenic bacteria [ Actinomycosis (G + ), E. Escherichia Coli − )] fungi ( Penicillium spp .) compared reference antibiotics, Chloramphenicol Nystatin. Furthermore, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) was used evaluate antioxidant activities its complex, showed they both possess significant properties comparison L‐ascorbic acid (Vit. C) standard. Based on docking studies, greater affinity (PDB ID: 3T88), corresponds coli protein (−6.7818 kcal/mol) (−6.7928 kcal/mol), respectively. Interestingly, most active inside site cervical cancer receptor 4XR8) higher binding energy (−6.2631 than free (−5.8561 kcal/mol). In silico, ADMET displayed obey Lipinski rule “Veber's rule. Consequently, likely exhibit oral bioavailability good LD 50 safety profile includes non‐cytotoxicity, non‐immunotoxicity, non‐skin sensitization. Finally, anticancer activity human cell lines HeLa SiHa positive controls (cisplatin) normal hepatic cells (WRL‐68). present study, all tested promising whose IC value ranged from (61.02 71.09) μg/mL.

Язык: Английский

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Discovery of novel pyrazole based Urea/Thiourea derivatives as multiple targeting VEGFR-2, EGFRWT, EGFRT790M tyrosine kinases and COX-2 Inhibitors, with anti-cancer and anti-inflammatory activities

Bioorganic Chemistry, Год журнала: 2024, Номер 147, С. 107403 - 107403

Опубликована: Апрель 27, 2024

Язык: Английский

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New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis

Bioorganic Chemistry, Год журнала: 2021, Номер 110, С. 104807 - 104807

Опубликована: Март 6, 2021

Язык: Английский

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New bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation

Bioorganic Chemistry, Год журнала: 2021, Номер 112, С. 104949 - 104949

Опубликована: Апрель 30, 2021

Язык: Английский

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Discovery of new anticancer thiourea-azetidine hybrids: design, synthesis, in vitro antiproliferative, SAR, in silico molecular docking against VEGFR-2, ADMET, toxicity, and DFT studies

Bioorganic Chemistry, Год журнала: 2021, Номер 115, С. 105206 - 105206

Опубликована: Июль 27, 2021

Язык: Английский

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New quinoxaline-2(1H)-ones as potential VEGFR-2 inhibitors: design, synthesis, molecular docking, ADMET profile and anti-proliferative evaluations

New Journal of Chemistry, Год журнала: 2021, Номер 45(36), С. 16949 - 16964

Опубликована: Янв. 1, 2021

Eleven new quinoxaline derivatives were designed and synthesized as modified VEGFR-2 inhibitors of our previous work.

Язык: Английский

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Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and in vivo studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2021, Номер 37(1), С. 299 - 314

Опубликована: Дек. 11, 2021

This research presents the design and synthesis of a novel series phthalazine derivatives as Topo II inhibitors, DNA intercalators, cytotoxic agents. In vitro testing new compounds against HepG-2, MCF-7, HCT-116 cell lines confirmed their potent activity with low IC50 values. inhibition intercalating activities were evaluated for most members. values determination demonstrated inhibitory affinities tested at micromolar level. Amongst, compound 9d was member. It inhibited enzyme value 7.02 ± 0.54 µM 26.19 1.14 µM. Compound then subjected to an in vivo antitumor examination. tumour proliferation reducing solid volume mass. Additionally, it restored liver enzymes, proteins, CBC parameters near-normal, indicating remarkable amelioration functions along histopathological examinations.

Язык: Английский

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New quinoline and isatin derivatives as apoptotic VEGFR-2 inhibitors: design, synthesis, anti-proliferative activity, docking, ADMET, toxicity, and MD simulation studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2022, Номер 37(1), С. 2191 - 2205

Опубликована: Авг. 16, 2022

New quinoline and isatin derivatives having the main characteristics of VEGFR-2 inhibitors was synthesised. The antiproliferative effects these compounds were estimated against A549, Caco-2, HepG2, MDA-MB-231. Compounds 13 14 showed comparable activities with doxorubicin Caco-2 cells. These strongly inhibited kinase activity. cytotoxic evaluated Vero Compound 7 highest value safety selectivity. Cell migration assay displayed ability compound to prevent healing abilities in cancer Furthermore, induced apoptosis through expressive down-regulation apoptotic genes, Bcl2, Bcl-xl, Survivin, upregulation TGF gene. Molecular docking emerged interactions synthesised a similar way sorafenib. Additionally, seven molecular dynamics simulations studies applied confirmed stability active pocket over 100 ns.

Язык: Английский

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Multi-Step In Silico Discovery of Natural Drugs against COVID-19 Targeting Main Protease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(13), С. 6912 - 6912

Опубликована: Июнь 21, 2022

In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, molecular structure similarity study done with PRD_002214, co-crystallized ligand Mpro (PDB ID: 6LU7), favored thirty Subsequently, fingerprint respect to PRD_002214 resulted election sixteen compounds (7, 128, 130, 156, 157, 158, 180, 184, 203, 204, 210, 237, 264, 276, 277, 278). Then, results docking versus PDB 6LU7 eight (128, 278) based on their binding affinities. toxicity studies for revealed that all them have good profiles. Finally, dynamic (MD) simulation experiments carried out 278, which exhibited best modes Mpro. MD tests luteoside (130) has greatest potential inhibit protease.

Язык: Английский

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