A comparative study of proapoptotic potential of cyano analogues of boswellic acid and 11-keto-boswellic acid

Semi-synthetic analogues of β-boswellic acid (BA) and 11-keto-β-boswellic acid (KBA) were comparatively evaluated for in vitro cytotoxicity against human myeloid leukaemia (HL-60) and human cervical carcinoma (HeLa) cells. 2-Cyano analogues of both the triterpenes were observed to have significant cytotoxicity against both the cells, displaying cytotoxicity in HL-60 cells at low concentrations. Further investigations suggested the proapoptotic potential associated with the two molecules to induce cytotoxicity in HL-60 cells, where one of them showed early proapoptotic effect as evidenced by several biological end-points of the apoptosis such as annexinV binding, DNA fragmentation and increase in sub-G0 DNA fraction and apoptotic bodies formation (Hoechst 33258 staining and SEM studies). A series of semi-synthetic analogues of BAs were comparatively evaluated for in vitro cytotoxicity against human cancer cell lines and their apoptotic potential. [Display omitted] ► Synthesis of cyanoenone analogues of boswellic acids. ► Evaluation of cytotoxicity against human myeloid leukemia (HL-60) and human cervical carcinoma (HeLa) cells. ► Identification of two leads displaying about 50-100 fold higher cytotoxicity than their parent molecules. ► The lead molecules were able to induce apoptosis evidenced by several biological endpoints. ► Further, one of the two leads induced strong and early apoptotsis.