title: Design and synthesis of resveratrol-based nitrovinylstilbenes as antimitotic agents.
abstract: A new series of resveratrol analogues was designed, synthesized, and demonstrated to be tubulin polymerization inhibitors. Most of these compounds exhibited antiproliferative activity and inhibited in vitro tubulin polymerization effectively at concentrations of 4.4-68.1 and 17-62 μM, respectively. Flow cytometry studies showed that compounds 7c, 7e, and 7g arrested cells in the G2/M phase of the cell cycle. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 7c and 7e. Docking of compounds 7c and 7e with tubulin suggested that the A-ring of the compounds occupies the colchicine binding site of tubulin, which coordinates with Cys241, Leu242, Ala250, Val318, Val328, and I378, and that the nitrovinyl side chain forms two hydrogen bonds with the main loop of the β-chain at Asn249 and Ala250.
authors.affiliation: Inorganic and Physical Chemistry Division , Indian Institute of Chemical Technology (Council of Scientific and Industrial Research), Hyderabad 500607, India.
authors.forename: M Amarnath
authors.initials: MA
authors.lastname: Reddy
authors.forename: Nishant
authors.initials: N
authors.lastname: Jain
authors.forename: Deepthi
authors.initials: D
authors.lastname: Yada
authors.forename: Chandan
authors.initials: C
authors.lastname: Kishore
authors.forename: Janakiram Reddy
authors.initials: JR
authors.lastname: Vangala
authors.forename: Reddy
authors.initials: R
authors.lastname: P Surendra
authors.forename: Anthony
authors.initials: A
authors.lastname: Addlagatta
authors.forename: Shasi V
authors.initials: SV
authors.lastname: Kalivendi
authors.forename: Bojja
authors.initials: B
authors.lastname: Sreedhar
mesh_terms: D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008958:Models, Molecular; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D050256:Antimitotic Agents; D009574:Nitro Compounds; D013267:Stilbenes; D050257:Tubulin Modulators; D014753:Vinyl Compounds; D053148:Caspase 3; D000077185:Resveratrol