Pictet-Spengler cyclization method has been adopted for the synthesis of three carboline derived compounds: two compounds with tetrahydro gama- and beta-having CF3 group and amino alkyl chain at delta and alpha position, respectively, and another with guanidine alkyl chain at alpha-position. Structure-activity relationship of the analogues with human serum albumin was studied by fluorescence and Fourier-transform infrared spectroscopy followed by molecular docking. The data showed maximum affinity of human serum albumin with comp7 (S0-820) followed by comp3 (S0-1040) and least with comp1 (S0-728). The compounds were tested for cytotoxic potencies. Comp3, showed maximum cytotoxicity with GI50 6.2 µM, against HCT-116, followed by comp7, and poor cytotoxicity with comp1. Comp3 and 7 induced oxidative stress mediated autophagy led programmed cell death in HCT-116. Furthermore, the compounds effectively inhibit DNA topoisomerase I activity and showed anti-inflammatory actions. In vivo studies regarding therapeutic protective action of Comp3, as a representative carboline analogue, against colon toxicant, 1,2-dimethylhydrazine dihydrochloride (DMH), showed the efficacy of the compound against organ toxicity. The existing studies on biological evaluation showed that these synthetic compounds may have a major role as anticancer agents having myriad of proven therapeutic applications. Communicated by Ramaswamy H. Sarma.
Keywords: Carboline derivative compounds; FTIR; autophagy; cell cytotoxicity; histology; human serum albumin (HSA); in vivo cytotoxicity; molecular docking.