| Abstract
| - In our search for potential new anticancer drugs, we designed and synthesized a series oftricyclic compounds containing the antimitotic 2-phenylazaflavone chromophore fused to apyrrole ring in a pyrroloquinoline structure. Compounds 8, 18, 19, 22, 23, 25 and 26, whentested against a panel of fourteen human tumor cell lines, showed poor in vitro cytotoxic activity,whereas 20, 21 and 24 showed significant activity (IC50 0.7 to 50 μM). Steroid hormone-sensitiveovary, liver, breast and adrenal gland adenocarcinoma cell lines displayed the highest sensitivity(IC50 0.7 to 8 μM). Compound 24 blocked cells in the G2/M phase of the cell cycle and induceda significant increase in apoptotis. Compounds 20, 21 and 24 proved to alter microtubuleassembly and stability, displaying a cytoplasmic microtubule network similar to that causedby Vincristine. In vivo, administration of compound 24 to Balb/c mice inhibited the growth ofa syngenic hepatocellular carcinoma.
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