1. 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies.
- Author
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Hagras M, Saleh MA, Ezz Eldin RR, Abuelkhir AA, Khidr EG, El-Husseiny AA, El-Mahdy HA, Elkaeed EB, and Eissa IH
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Proliferation drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Molecular Docking Simulation, Molecular Structure, Naphthalenes chemical synthesis, Naphthalenes chemistry, Oxadiazoles chemical synthesis, Oxadiazoles chemistry, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Structure-Activity Relationship, Vascular Endothelial Growth Factor Receptor-2 metabolism, Antineoplastic Agents pharmacology, Drug Design, Naphthalenes pharmacology, Oxadiazoles pharmacology, Protein Kinase Inhibitors pharmacology, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
- Abstract
In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity ( 5 , 8 , 15 , 16 , 17 , and 18 ) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.
- Published
- 2022
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