QUINOXALINE CHEMISTRY - PART 11 - 3-PHENYL-2[PHENOXY- AND PHENOXYMETHYL]-6(7) OR 6,8-SUBSTITUTED QUINOXALINES AND N-[4-(6(7)-SUBSTITUTED OR6,8-DISUBSTITUTED-3-PHENYLQUINOXALIN-2-YL)HYDROXY OR HYDROXYMETHYL]BENZOYLGLUTAMATES - SYNTHESIS AND EVALUATION OF IN-VITRO ANTICANCER ACTIVITY AND ENZYMATIC INHIBITORY ACTIVITY AGAINST DIHYDROFOLATE-REDUCTASEAND THYMIDYLATE SYNTHASE

Twenty-four out of twenty-nine quinoxalines were selected at the Natio nal Cancer Institute, Bethesda, Md, USA, for in vitro anticancer scree ning. Among these, 10 derivatives exhibited high values of percent tum or growth inhibition at a concentration of 10(-4) M in all cancer cell lines. Four of these compounds maintained these values at 10(-5) M, w hereas a certain number exhibited significant values of percent inhibi tion at the most diluted concentrations (10(-8)-10(-6) M). Inhibitory activity against dihydrofolate reductase (DHFR) (bovine and rat liver) was determined for the most active compounds. This test showed that t his type of quinoxaline exhibited an appreciable activity in compariso n with the previously described aza analogues. In the other test (Lact obacillus casei, thymidylate synthase (TS), human HTS) no or poor acti vity was detected in both series of compounds. (C) 1998 Elsevier Scien ce S.A. All rights reserved.