13023-74-0Relevant articles and documents
Targeting receptor tyrosine kinase VEGFR-2 in hepatocellular cancer: Rational design, synthesis and biological evaluation of 1,2-disubstituted benzimidazoles
Abdel-Mohsen, Heba T.,Abdullaziz, Mona A.,Ali, Mamdouh M.,El Diwani, Hoda I.,El Kerdawy, Ahmed M.,Flanagan, Keith J.,Mahmoud, Abeer E. E.,Ragab, Fatma A. F.,Senge, Mathias O.
, (2020)
In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as VEGFR-2 inhibitors targeting hepatocellular carcinoma. Our design strategy is twofold; it aimed first at studying the effect of replacing the 5-methylfuryl moiety of the well-known antiangiogenic 2-furylbenzimidazoles with an isopropyl moiety on the VEGFR-2 inhibitory activity and the cytotoxic activity. Our second objective was to further optimize the structures of the benzimidazole derivatives through elongation of the side chains at their one-position for the design of more potent type II-like VEGFR-2 inhibitors. The designed 1,2-disubstituted benzimidazoles demonstrated potent cytotoxic activity against the HepG2 cell line, reaching IC50 = 1.98 μM in comparison to sorafenib (IC50 = 10.99 μM). In addition, the synthesized compounds revealed promising VEGFR-2 inhibitory activity in the HepG2 cell line, e.g., compounds 17a and 6 showed 82% and 80% inhibition, respectively, in comparison to sorafenib (% inhibition = 92%). Studying the effect of 17a on the HepG2 cell cycle demonstrated that 17a arrested the cell cycle at the G2/M phase and induced a dose-dependent apoptotic effect. Molecular docking studies of the synthesized 1,2-disubstituted benzimidazoles in the VEGFR-2 active site displayed their ability to accomplish the essential hydrogen bonding and hydrophobic interactions for optimum inhibitory activity.
STUDY OF THE HYDROLYTIC STABILITY OF 1-ANILINO-1-ALKANESULFONATES BY MEANS OF SPECTRODENSITOMETRIC THIN-LAYER CHROMATOGRAPHY
Nesterenko, S. A.,Bogatchuk, Yu. Ya.,Kofanov, V. I.
, p. 1666 - 1670 (2007/10/02)
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