Cu-promoted synthesis of Indolo[2,3-b]quinoxaline-Mannich adducts via three-component reaction and their anti-proliferative evaluation on colorectal and ovarian cancer cells.

• Cu-promoted synthesis of indolo [2,3- b ]quinoxaline-Mannich adducts. • The anti-proliferative activities were assessed on OVCAR-3 and HT-29 cells. • The promising compounds exhibited caspase-mediated apoptotic cell death. • The promising compounds were further studied in silico using the crystal structure of c-Met-kinase. The present work intends to synthesize a new class of small molecules featuring the quinoxaline scaffold. The indolo [2,3- b ]quinoxaline-Mannich adducts were designed, synthesized and their anticancer activities were tested using MTS assay against human ovarian cancer (OVCAR-3) and female colorectal adenocarcinoma cancer cell lines (HT-29). Compounds 6q and 6r efficiently inhibited both cancer cell lines tested, with IC 50 values of 58.57 and 55.90 µM against OVCAR-3 and 31.36 and 42.3 µM against HT-29, respectively. The evaluation results were further supported by caspase-mediated apoptosis and docking studies, which indicated that Tyr1159 and the N-atom of the pyrrolidine moiety formed an additional hydrogen bond that stabilised the c-Met-kinase-6q complex. Overall, the results of our study suggested that Mannich-inspired indolo [2,3- b ]quinoxaline adduct might make interesting lead for the development of cancer chemotherapeutics. Synthesis and anti-proliferative evaluation of Indolo [2,3- b ]quinoxaline-Mannich adducts [Display omitted] [ABSTRACT FROM AUTHOR]