title: Design and synthesis of biaryl aryl stilbenes/ethylenes as antimicrotubule agents.
abstract: Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. A common intermediate 4,5,6-trimethoxybiphenyl-2-carbaldehydes was employed to generate the two scaffolds. Majority of the analogs inhibited cell proliferation and those functionalized with 3,4-(1,3-dioxolane) and 3,4-difluoro groups were identified as effective inhibitors in both the series. Treatments with 19b, 19c, 22b and 22c arrested cells at G2/M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2/M marker, Cyclin B1. Molecular docking analysis demonstrated the interaction of these compounds at the colchicine binding site of tubulin.
authors: Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology (Council of Scientific and Industrial Research), Hyderabad 500607, India.
authors: A Suresh
authors: AS
authors: Kumar
authors: M Amarnath
authors: MA
authors: Reddy
authors: Nishant
authors: N
authors: Jain
authors: Chandan
authors: C
authors: Kishor
authors: T Ramalinga
authors: TR
authors: Murthy
authors: Deepa
authors: D
authors: Ramesh
authors: Bhukya
authors: B
authors: Supriya
authors: Anthony
authors: A
authors: Addlagatta
authors: Shasi V
authors: SV
authors: Kalivendi
authors: B
authors: B
authors: Sreedhar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005030:Ethylenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005030:Ethylenes; D013267:Stilbenes