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The triple-negative breast cancer cell line MDA-MB-231 has been known as one of the most tenacious cancer cancer cells and paid attention by many researchers. A two-dimension quantitative structure-activity relationship (2D-QSAR) model of 131 benzimidazole derivatives was developed to relate the chemical–biological interactions and predicted the half maximal inhibitory concentration (IC50) against MDA-MB-231 cell line. The 2D-QSAR model was obtained satisfactory internal and external validation parameters such as the square of correlation coefficient R2 = 0.904 and concordance correlation coefficient CCC = 0.867. The model was and applied on 35 synthesized benzimidazoles to predict IC50 values. The results showed that benzimidazoles with IC50 less than 50 µM displayed a quite similarity between predicted and experimental IC50 values (Ra2 = 0.924). The molecular docking study was investigated to clarify the binding mode of the most potential synthesized benzimidazoles (BLMM, and BL3H) into topoisomerase I-DNA complex. The docking results revealed that they intercalated and interacted to crucial amino acids in the binding site of complex by hydrogen bonds and hydrophobic interactions and compared to standard drug camptothecin.

This study reports a simple process to synthesize and separate of 2-(substituted-phenyl) benzimidazole derivatives with high yield and efficiency. Specifically, by reacting ortho-phenylenediamines with benzaldehydes using sodium metabisulphite as an oxidation agent in a mixture of solvent under mild condition, twenty-three compounds of benzimidazoles were obtained and separated easily using hexane and water to wash, respectively. The structure of all obtained compounds was identified by FTIR, NMR and HRMS. The SAR analysis of synthesized benzimidazoles on human lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cell lines showed that the presence of methyl group at 5(6)-position on benzimidazole scaffold was a contributing factor influencing the anticancer activity. The presence of electron-donating groups (OH, OMe, –NMe2, –O–CH2–C6H5) also caused significant increase of anticancer activity, while the presence of electron-withdrawing groups (–NO2, –CF3) on the phenyl group at 2-position of benzimidazole ring decreased the ability of inhibition of synthesized benzimidazoles. The compounds 2f and 2g displayed the significant anticancer activity on both A549 and PC3 cell lines. Two series of 2-phenylbenzimidazoles were synthesized by simple process with high yield and efficiency and they were illumiated the effect of substituent groups in their structures on the bioactivity against three cancer cell line A549, MDA-MB-231 and PC3.

In order to explore and develop new anticancer agents, three series of 2-phenylbenzimidazoles, 15–46, were condensed under simple and mild conditions using sodium metabisulfite as an oxidation agent and another series, 47–55, were obtained via a reduction reaction using sodium borohydride. All the compounds synthesized were evaluated for their in vitro anticancer activities against three human cancer cell lines. The novel compound 38 was found to be the most potent multi cancer inhibitor against A549, MDA-MB-231, and PC3 cell lines (IC50 values 4.47, 4.68 and 5.50 μg mL−1, respectively). In addition, compound 40 exhibited the best IC50 value of 3.55 μg mL−1 against the MDA-MB-231 cell line. The results demonstrated that introducing a new substituent to compounds 37–55 could improve their antiproliferative activities.

Discovering and developing drugs to treat Alzheimer's disease (AD) have been a crucial target for many decades. According to a large number of later studies, acetylcholinesterase (AChE) plays an important role in AD treatment. On the other hand, flavonoids are natural compounds that possessed a wide variety of bioactivities, including the inhibitory activity on AChE. In this study, we reported the structure and activity relationship of flavone and flavanone derivatives that semi-synthesized and synthesized from flower buds of Styphnolobium japonicum (Leguminosae) and citrus peels against AChE. The results showed that the introducing of the new functional groups that leads to increasing 3-folds better AChE inhibition of compound Q2 and Q4 than that of the original. The molecular docking study was investigated in order to illuminate the experimental results and find their binding modes.