title: Synthesis and biological evaluation of 4β-acrylamidopodophyllotoxin congeners as DNA damaging agents.
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.
authors: Division of Organic Chemistry, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India. ahmedkamal@iict.res.in
authors: Ahmed
authors: A
authors: Kamal
authors: Paidakula
authors: P
authors: Suresh
authors: M
authors: M
authors: Janaki Ramaiah
authors: Adla
authors: A
authors: Mallareddy
authors: Banala Ashwini
authors: BA
authors: Kumar
authors: Paidakula
authors: P
authors: Raju
authors: J
authors: J
authors: Vinay Gopal
authors: S N C V L
authors: SN
authors: Pushpavalli
authors: A
authors: A
authors: Lavanya
authors: Pranjal
authors: P
authors: Sarma
authors: Manika
authors: M
authors: Pal-Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D020552:Comet Assay; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D004247:DNA; D011034:Podophyllotoxin