Antitumor Agents. 150. 2′,3′,4′,5′,5,6,7-Substituted 2-Phenyl-4-quinolones and Related Compounds: Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization

As part of our continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, we have synthesized a series of 6,7-methylenedioxy-substituted and unsubstituted 2-phenyl-4-quinolones, as well as related compounds. Their in vitro inhibition of human tumor cell lines and tubulin polymerization is reported. In general, a good correlation was found between cytotoxicity and inhibition of tubulin polymerization. Compounds 7, 9, 13, 16, 22, 23, 36, and 37 showed potent inhibitory effects in both assays. All rigid analogs (47–49) and trimethoxy-substituted compounds showed little or no activity. Substitution at the 4′-position also resulted in compounds with little or no activity, except for hydroxyl or methyl groups at this position. Further investigation is underway to determine if substitution at the 3′-position will result in compounds with increased activity.