fosbretabulin and imidazolone

A series of novel combretastatin-A4 analogues in which the cis-olefinic bridge is replaced by an imidazolone-amide were synthesized, and their cytotoxicity and tubulin-polymerization inhibitory activities were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 10, 9b and 9c, bearing 3'-NH₂-4'-OCH₃, 4'-CH₃ and 3'-CH₃-substituted 1-phenyl B-ring, confer optimal bioactivity. The binding modes of these compounds to tubulin were obtained by molecular docking, which can explain the compounds' structure-activity relationship. The studies presented here provide a new structural type for the development of novel antitumor agents.

Topics: Amides; Binding Sites; Cell Line, Tumor; Computer Simulation; Humans; Imidazoles; Isomerism; Stilbenes; Structure-Activity Relationship; Tubulin; Tubulin Modulators

A series of novel chalcone linked imidazolones were prepared and evaluated for their anti-cancer activity against a panel of 53 human tumour cell lines derived from nine different cancer types: leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate and breast. Some of these hybrids (6, 7 and 8) showed good anti-cancer activity with GI(50) values ranging from 1.26 to 13.9 microM. When breast carcinoma cells (MCF-7) were treated with 10 microM concentration of compounds TMAC, CA-4, 6 and 8 cell cycle arrest was observed in G2/M phase. Surprisingly, the increased concentration of the same compound to 30 microM caused accumulation of cells in G0/G1 phase of the cell cycle.

Topics: Antineoplastic Agents; Cell Line, Tumor; Chalcone; Drug Screening Assays, Antitumor; Humans; Imidazoles; Neoplasms