Synthesis and Characterization of Novel N-Benzylbenzimidazole Linked Pyrimidine Derivatives as Anticancer Agents

Abstract

Background: Emergence of resistance to accessible anticancer drugs became a threat to human lives in the recent time. To address this issue, discovery of novel anticancer agents becomes very essential. Benzimidazoles and pyrimidines have been reported to possess potent anticancer activity. Materials and Methods: A hybrid approach has been used, in which core structure of potentially active N-benzyl benzimidazole and pyrimidine derivatives are brought together in to a single molecule. The desired compounds were prepared by the condensation of N-benzyl benzimidazole chalcones with guanidine hydrochloride. The synthesized compounds were characterized using spectral studies (IR, 1 H, 13 C-NMR techniques and mass spectrometry). All the compounds were screened for their anticancer activity against human breast cancer cell line MDA-MB-231. Results: The spectral data's are in well agreement with the synthesized compounds 5a-e. Compounds 5b (GI 50 = 39.6 μM) and 5a (GI 50 =84.0 μM) exhibited significant anticancer activity. Conclusion: Owing to the anticancer activity, compound 5b can be used as lead structure in the development of yet more potent anticancer agents.

Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure–activity relationship, and mechanisms of action (2019–2021)

“…[98] The SAR illustrated that the linker between benzimidazole and pyrimidine moieties influenced the activity remarkably and thioether linker was more favorable than the amino linker. [98][99][100][101] Among them, hybrids 44 (Figure 8; IC 50 : 6.5-10.4 µM, MTT assay) and 45 (IC 50 : 2.2-7.3 µM, MTT assay) were found to be most active in each series and hybrid 45 was comparable to nocodazole (IC 50 : 2.0-3.5 µM), whereas hybrid 46 (inhibitory rate: 32.7%-88.4% at 10.0 µM, SRB assay) possessed broad-spectrum activity against a panel of 25 cancer cell lines. Mechanistically, hybrid 45 impaired migration, inhibited the colony formation, arrested the G2/M phase, enhanced microtubule disruption, inhibited tubulin polymerization, and induced apoptosis with triggering of ROS generation and loss of mitochondrial membrane potential.…”