title: Part I. Synthesis, biological evaluation and docking studies of new 2-furylbenzimidazoles as antiangiogenic agents.
abstract: 2-(2-Furyl)-1H-benzimidazoles 3-11 were synthesized and tested for their in vitro VEGF inhibition in MCF-7 cancer cell line. Compound 5a was more potent than Tamoxifen, and compounds 3b, 5a, 5c, 6b, 7a and 10 showed promising potency. Furthermore, compounds (6b, 7a and 10) showed remarkable selective inhibition of COX-2 enzyme close to that of Celecoxcib. Additionally, docking studies were performed using AutoDock 4.2 into the VEGFR2 kinase. Significant correlation exists between the biological activity (IC50 and %VEGF inhibition) against MCF-7 cell line and the molecular docking results (Ki and ΔGb) with correlation coefficients (R(2)) of 0.5513 and 0.4623 respectively. Accordingly, most of the synthesized 2-(2-furyl)-1H-benzimidazoles showed strong antiangiogenic activity against VEGFR2 kinase.
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Temirak
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt. Electronic address: yabdelrahman@yahoo.com.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Shaker
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Fatma A F
authors.initials: FA
authors.lastname: Ragab
authors.affiliation: Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, 12622 Cairo, Egypt.
authors.forename: Mamdouh M
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, TX, USA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors.forename: Hamed I
authors.initials: HI
authors.lastname: Ali
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt.
authors.forename: Hoda I
authors.initials: HI
authors.lastname: El Diwani
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D062105:Molecular Docking Simulation; D066244:Proton Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
chemical_list: D020533:Angiogenesis Inhibitors; D001562:Benzimidazoles
keywords: 2-(2-Furyl)-1H-benzimidazoles; Angiogenesis; Cytotoxicity; VEGFR2 kinase; Vascular endothelial growth factor (VEGF)