Synthesis and biological evaluation of 4β-acrylamidopodophyllotoxin congeners as DNA damaging agents.
Basic Information
ID: ALA1811806
Journal: Bioorg Med Chem
Title: Synthesis and biological evaluation of 4β-acrylamidopodophyllotoxin congeners as DNA damaging agents.
Authors: Kamal A, Suresh P, Janaki Ramaiah M, Mallareddy A, Kumar BA, Raju P, Vinay Gopal J, Pushpavalli SN, Lavanya A, Sarma P, Pal-Bhadra M.
Abstract: A series of new 4β-acrylamidopodophyllotoxin derivatives (13a-o) were synthesized by coupling of substituted acrylic acids (10a-l and 11m-o) to the 4β-aminopodophyllotoxin. The synthesized derivatives 13a-o were evaluated for their cytotoxicity against five human cancer cell lines (breast, oral, colon, lung and ovarian). These podophyllotoxin conjugates have shown promising activity with GI₅₀ values ranging from <0.1 to 0.29 μM. Some of the compounds 13j, 13k and 13l that showed significant antiproliferative activity were also evaluated for related cytotoxic effects in MCF-7 cells, and compared to etoposide. These compounds (13j, 13k and 13l) showed G2/M cell cycle arrest and the apoptotic event was found to be due to both the single-strand DNA breaks as observed by comet assay as well as double-strand breaks as observed by the large accumulation of gamma H2AX foci.
CiteXplore: 21737288
DOI: 10.1016/j.bmc.2011.06.017
Patent ID: ┄