Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities.

ABSTRACT: A new series of phenolic glycoside esters, saccharumoside-B and its analogs (9b-9n, 10) have been synthesized by the Koenigs-Knorr reaction. Antiproliferative activities of the compounds (9b-9n, 10) were evaluated on various cancer cell lines including, MCF-7 breast, HL-60 leukemia, MIA PaCa-2 pancreatic, DU145 prostate, HeLa cervical and CaCo-2 colon, as well as normal human MCF10A mammary epithelial and human peripheral blood mononuclear cells (PBMC) by MTT assay. Compounds (9b-9n, 10) exhibited considerable antiproliferative effects against cancer cells with IC₅₀ range of 4.43?±?0.35 to 49.63?±?3.59?µM, but they are less cytotoxic on normal cells (IC₅₀?>?100?µM). Among all the compounds, 9f showed substantial antiproliferative activity against MCF-7 and HL-60 cells with IC₅₀ of 6.13?±?0.64 and 4.43?±?0.35, respectively. Further mechanistic studies of 9f were carried out on MCF-7 and HL-60 cell lines. 9f caused arrest of cell cycle of MCF-7 and HL-60 cells at G0/G1 phase. Apoptotic population elevation, mitochondrial membrane potential loss, increase of cytosolic cytochrome c and Bax levels, decrease of Bcl-2 levels and enhanced caspases-9 and -3 activities were observed in 9f-treated MCF-7 and HL-60 cells. These results demonstrate anticancer and apoptosis-inducing potentials of 9f in MCF-7 and HL-60 cells via intrinsic pathway.

SUBMITTER: Rayavarapu S 

PROVIDER: S-EPMC5559490 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature