ANTITUMOR AGENTS .166. SYNTHESIS AND BIOLOGICAL EVALUATION OF 5,6,7,8-SUBSTITUTED-2-PHENYLTHIOCHROMEN-4-ONES

As a continuation of our structure-activity relationship study of subs tituted 2-phenyl-4-quinolones and flavonoids as antitumor and antivira l agents, a series of 5,6,7,8-substituted-2-phenylthiochromen-4-ones h as been synthesized by condensation of substituted thiophenols and eth yl benzoylacetates. Target compounds were evaluated for biological act ivity. Among them, compounds 7, 10, 12, and 13 displayed significant g rowth inhibitory action against a panel of tumor cell lines including human ileocecal carcinoma (HCT-8), murine leukemia (P-388), human mela noma (RPMI), and human central nervous system tumor (TE671) cells. Com pounds 10, 12, and 19 displayed DNA topoisomerase I inhibitory activit y in vitro and compound 11 was an in vitro, inhibitor of DNA topoisome rase II. Compound 11 was most active (ED(50) value, 0.65 mu M) against HIV in acutely infected H9 lymphocytes and had a therapeutic index of about 5.