title: Synthesis and antitumor evaluation of nitrovinyl biphenyls: anticancer agents based on allocolchicines.
abstract: A new class of nitrovinyl biphenyl compounds based on the structures of colchicines and allocolchicines were designed, synthesized, and shown to inhibit tubulin polymerization and cause mitotic arrest. A majority of these compounds were found to possess potent anticancer properties, with IC(50) values in the range of 0.05-7 μM, and are equally potent with colchicine in HeLa and MCF-7 cells. Compounds 14 e and 14 f inhibited tubulin assembly by more than 60 %, and flow cytometry studies indicated growth arrest of cells in the G(2)/M phase of the cell cycle in a concentration-dependent manner. Treatment of cells with 14 f resulted in upregulation of cyclin B1 and aurora kinase B mRNA levels, corresponding to growth arrest in the G(2)/M phase of the cell cycle as the mode of action.
authors.affiliation: Centre for Chemical Biology, Indian Institute of Chemical Technology (Council of Scientific and Industrial Research), Hyderabad, India.
authors.forename: Nishant
authors.initials: N
authors.lastname: Jain
authors.forename: Divya
authors.initials: D
authors.lastname: Yada
authors.forename: Thokhir B
authors.initials: TB
authors.lastname: Shaik
authors.forename: Galanki
authors.initials: G
authors.lastname: Vasantha
authors.forename: P Surendra
authors.initials: PS
authors.lastname: Reddy
authors.forename: Shasi V
authors.initials: SV
authors.lastname: Kalivendi
authors.forename: B
authors.initials: B
authors.lastname: Sreedhar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001713:Biphenyl Compounds / Q000737:chemistry*; D002455:Cell Division; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001713:Biphenyl Compounds; D003078:Colchicine; D056744:Cyclin B1; D017346:Protein Serine-Threonine Kinases; D014404:Tubulin; D050257:Tubulin Modulators; C010574:biphenyl; C032782:allocolchicine; C576921:AURKB protein, human