Synthesis and antitumor activity of a series of sulfone analogues of 1,4-naphthoquinone.
A series of novel substituted thiochromones and thiochroman-4-ones was synthesized. Compounds were designed as analogues of naphthoquinone and as potential "bioreductive alkylating agents" and were tested for antitumor activity. The lead compound, 3-(chloromethyl)thiochromone 1,1-dioxide (4), inhibited Ehrlich ascites tumor growth by 100% in CF1 male mice at 10 (mg/kg)/day ip. Similarly, 18 of the 29 related compounds demonstrated good activity in this tumor screen. Few definitive structure-activity correlations were evident regarding the nature of the 3-substituent. However, the 2,3 double bond and a sulfone or sulfoxide were required for activity. Four of the compounds synthesized showed marginal but significant activity against P-388 lymphocytic leukemia.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D003499:Cyclic S-Oxides; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice
D000970:Antineoplastic Agents; D003499:Cyclic S-Oxides; C031794:3-(chloromethyl)thiochromone 1,1-dioxide