Design, synthesis and biological evaluation of chrysin benzimidazole derivatives as potential anticancer agents

Abstract

A series of chrysin benzimidazole derivatives were synthesised and evaluated for their anticancer activity in the search for potential anticancer agents. Among them, compound 18 displayed the most potent anti-proliferative activity against MFC cells with IC values of 25.72 ± 3.95 μM. The flow cytometry results displayed that compound 18 induced apoptosis of MFC cells in a dose-dependent manner and caused the cell cycle to be arrested in the G0/G1 phase. Furthermore, the preliminary anticancer activity in vivo was also studied in tumour-bearing mice, and the compound 18 exerted good inhibition effect on tumour growth. These results suggested that compound 18 had good anticancer activity, which could be a potential anticancer agent after further optimisation and evaluation.

Significance of Benzimidazole analogues for the creation of novel molecules in drug discovery

“…Compounds (39) possesses highly potent antiviral activity. (39) In the year 1999, Pandey and Shukla 29 prepared 7-(arylamidoalkyl)-3,4-diphenyl-isoquinolinyl-[1,5-c]-benzimidazoles derivatives which were screened against influenza virus in vitro and the virus was inoculated in hen's egg at allantoic cavity. The results revealed that the nicotinamido group is essential for isoquinonyl benzimidazole derivatives.…”

Benzimidazole: Pharmacological Profile

“…In the year of 2019 Tahlan et al, reported the synthesis and anti cancer activity of the new benzimidazole derivatives, among all the derivatives the compound 1 (Figure 3) found to be best activity at IC 50 value of 4.53 μM against the human colorectal cancer cell line [4], same authors in 2018 reported the compound 2 (Figure 3) showed best activity at IC 50 value of 4.12 μM against the human colorectal carcinoma cell line (HCT116) [18], same year few authors reported the synthesis, anti anti cancer activity of the new benzimidazole derivatives, Aikman et al, reported the compound 3 (Figure 3) found to be best active compound at EC50 value of 5 AE 2 μM against the melanoma (A375) cells [19], Mohamed et al, reported the compound 4 (Figure 3) showed best activity at IC 50 value of 80,35, 72 μg/ml against the against human breast adenocarcinoma (MCF-7), human lung carcinoma (A549), human epitheloid cervix carcinoma (HELA) [20], Gohary et al, reported the compound 5 (Figure 3) showed significant activity at IC 50 value of 0.022, 0.014, 0.015 μM against the against liver cancer (HepG2), colon cancer (HCT-116), breast cancer (MCF-7) cells [21], in 2017 Wang et al, reported the synthesis, anti-cancer activity of the chrysin benzimidazole derivatives, the compound 6 (Figure 3) showed significant activity at IC 50 values of 25.72 AE 3.95 μM against MFC cells [22] and Yadav et al, reported the anti cancer activity of synthesized the 2-(1H-benzo[d]imidazol-2-ylthio)acetami do)-N-(substituted-4oxothiazolidin-3-yl)acetamides, the compound 7, 8 (Figure 3) showed significant activity at IC 50 value of 0.00005, 0.00012 μM/ml against HCT116 cell line [23], Onnis et al, reported the anti cancer activity of benzimidazolehydrazones, the compound 9 (Figure 3) showed excellent activity at IC 50 value of 0.98 AE 0.02 μM against human T-lymphoblastic leukemia (CEM) cells [24].…”

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

“…Sharma et al ( Sharma P. et al, 2017 ) designed and synthesized a series of benzimidazole bearing thiazolidinedione derivatives, and proved remarkable cytotoxicity of these compounds ( 254–256) towards PC-3, HeLa, A549 and HT1080 cancer cell lines with IC 50 values of 0.096–0.63 µM. In a different study, Compound 257 exhibited potent antiproliferative effect against MFC cells IC 50 (mean ± SD) value of 25.72 ± 3.95 μM ( Wang et al, 2017 ). Triazole containing 4,5,6,7-tetrabromo-1 H -benzimidazole derivatives 258–259 bearing carboxyl substituent manifested the most prominent inhibitory effect against protein kinase 2 (CK2) with binding affinity value in the range of 1.96–0.91 µM ( Chojnacki et al, 2017 ).…”