Design, synthesis, anti-cancer evaluation and binding mode studies of benzimidazole/benzoxazole linked β-carboline derivatives

•We have design and synthesized a new series of benzimidazole/benzoxazole linked β-Carboline derivatives.•All these derivatives are screened for their anticancer activities against MCF-7 (breast), A549 (lung), Colo-205 (colon) and A2780 (ovarian) by using standard MTT assay.•The compound 9b showed promising anticancer activities against MCF-7 cell line with IC50 value of 0.092±0.001 µM.•The anti-cancer data of new hybrid β-carbolines against MCF-7 cell lines are in agreement with parent β-carboline skeleton. A new series of benzimidazole/benzoxazole linked β-carbolines (9a-j) were rationally designed and synthesized by combining two different anti-cancer fragments. The new hybrid β-carbolines are subjected to anti-cancer screening against four different human cancer cell lines such as MCF-7 (breast), A549 (lung), Colo-205 (colon) and A2780 (ovarian) by using standard MTT assay. These hybrid β-carbolines exhibited significant and high fold anti-cancer activity against MCF-7 cell lines than reference standard. They are also proved to be effective against A549 and Colo-205 cell lines. Further, compound 9b, 9c from benzimidazole and 9i from benzoxazole series have exhibited maximum anti-cancer activity among these hybrid β-carbolines. Later, all of the hybrid β-carbolines were subjected to molecular interaction analysis against a few selected kinase targets such as cdc-like kinase (CLK-1 to CLK-4), epidermal growth factor reductase (EGFR) kinase, protein (ATR) kinase along with APC-Asef interface. The violin plot of binding energies of 9a-9j have suggested them as good kinase binders. Result interpretation suggested hybrid β-carbolines as promising CLK binders. The anti-cancer data of new hybrid β-carbolines against MCF-7 cell lines are in agreement with parent β-carboline skeleton. [Display omitted] It is informed to your kind notice that All authors have a responsibility to disclose interests that might appear to affect their ability to present data objectively. We have no any conflict of interest statement.