Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent and Evaluation for CDK2 Inhibition Activity

Abstract

Background: Thiobezimidazoles reveal various pharmacological activities due to similarities with many natural and synthetic molecules, they can easily interact with biomolecules of living systems. Objective: A series of substituted 2-thiobezimidazoles has been synthesized .Twelve final compounds were screened for in vitro anti-cancer activities against sixty different cell-lines. Methods: The spectral data of the synthesized compounds were characterized. Docking study for active anticancer compounds and CDK2/CyclinA2 Kinase assay against standard reference; Imatinib were performed. Results: Two compounds (3c&3l) from the examined series revealed effective antitumor activity in vitro against two-cancer cell lines (Colon Cancer (HCT-116) and Renal Cancer (TK-10). The docking study of synthesized molecules discovered a requisite binding pose in CDK-ATP binding pocket. 3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. Conclusion: Against all tested compounds ; two compounds 3c &3l were found active against two types of cell-lines.

Novel 1,2,5-Trisubstituted Benzimidazoles Potentiate Apoptosis by Mitochondrial Dysfunction in Panel of Cancer Cells

“…The literature survey revealed that the benzimidazole derivatives have been extensively investigated as potential anticancer agents, and these benzimidazole derivatives exhibit anticancer effects through different mechanisms of action such as intercalating mode of action (DNA binding), nonintercalating mode of action (topoisomerases inhibition), DNA alkylation (DNA cleavage), acting on enzyme antimetabolites [DihydrofolateReductase (DHFR) inhibition], sirtuin inhibition (SIrt1 and SIrt2 inhibition), acting on structural proteins (tubulin protein inhibition), and protein kinase inhibition. − …”

“…NMR spectra of intermediates and final compounds 2, 3a, 3b, 3c, 4a, 4b, 4c, and TJ01−TJ15;13 C NMR spectra of the final compounds TJ01−TJ15; HRMS spectra of the final compounds TJ01−TJ15; LC−MS spectra of intermediates and final compounds 2, 3a, 3b, 3c, 4a, 4b, 4c, and TJ01−TJ15; FT-IR spectra of the final compounds TJ01−TJ15 (PDF) ■ AUTHOR INFORMATION Corresponding Authors…”

“…13 C NMR (100 MHz, DMSO-d 6 ) δ: 167 24,. 162.74 (d, J C−F = 242 Hz), 157.76, 156.01, 142.25, 139.05, 133.05, 131.18, 131.10, 130.90, 128.82, 125.90, 123.43, 123.39, 120.81, 120.62, 115.84, 115.63, 111.06, 110.48, 55.63, 52.38, 43.85, 32.36, 30.60.…”

“…−OCH 3 ) 13. C NMR (100 MHz, DMSOd 6 ) δ: 167.00, 157.23 (d, J C−F = 264 Hz), 152.75, 142.45, 139.86, 137.48 (d, J C−F = 25 Hz), 137.40, 137.33, 136.72, 129.37, 128.20, 127.39, 127.37, 127.11, 127.07, 126.69, 124.74, 124.71, 121.66, 119.95 (d, J C−F = 21 Hz), 111.99, 52.57, 48.28.…”

“…J = 6.6 Hz, 2H, −CH 2 ), 5.66 (s, 2H, −CH 2 ) 13. C NMR (100 MHz, DMSO-d 6 ) δ: 168.17, 153.80, 153.60, 142.52, 139.70, 137.36, 136.94, 135.80, 129.35, 128.89, 128.11, 127.12, 126.60, 126.45, 125.66, 124.59, 121.44, 120.86, 120.14, 111.48, 48.22.…”