New Benzimidazoles and Their Antitumor Effects with Aurora A Kinase and KSP Inhibitory Activities

Abstract

A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and (1) H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition.

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

“…The benzimidazole-thiazole derivatives 231–232 showed notable anticancer effect against human liver carcinoma cell line (HepG2: IC 50 = 0.518 and 0.578 mM) and pheochromocytoma of the rat adrenal medulla cell line (PC12: IC 50 = 0.309 and 0.298 mM) ( Nofal et al, 2014 ). Compounds 233–234 with dual inhibition of Aurora A kinase and kinesin spindle protein were found to be the most prominent antitumor agents against various tested cell lines in comparison with standard drug CK0106023 ( Abd El-All et al, 2015 ). Kalalbandi and Seetharamappa synthesized a series of 1-[(2 E )-3-phenylprop-2-enoyl]-1 H -benzimidazole derivatives among which compound 235 displayed notable antiproliferative activity against nine tumor subpanels, indicated by its selectivity ratios within the range of 0.79–1.53 and 0.47 to 1.69 at the GI 50 (growth inhibitory 50%) and TGI level, respectively ( Kalalbandi and Seetharamappa, 2015 ).…”

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“…survival adhesion, migration, and differentiation. Overexpression or overactivity of this EGFR because of mutations that lead to a variety of human cancers such as lung, colon, and breast cancers 9,10 . The binding of a ligand to EGFR induces conformational changes within the receptor, which increase its intrinsic catalytic activity of a tyrosine kinase and result in autophosphorylation, which is necessary for biological activity.…”

Synthesis of 1, 2, 3-triazolo-piperazines compounds and their screening for Anticancer activity using C6 Glioma cell lines

“…Heterocycles containing Nitrogen comprising of triazoles, benzothiazoles, benzimidazoles, indoles, etc. constitute an important scaffold in biological science and medicinal chemistry, and has fascinating applications in drug discovery and development [1][2][3][4][5] . In particular, the synthesis of 1, 2, 3-triazoles has attracted considerable attention during the last years.…”