Synthesis and novel bioactivities of substituted 6-propylthiouracils

Abstract

The synthetic design and novel bioactivities of substituted 6-n-propylthiouracils are reported. The target compounds were accomplished via base catalyzed alkylation (using RBr) of 6-n-propyl-2-thiouracil. The alkylation occurred primarily at a thione moiety to form S-substituted uracils 2a-d (R = n-C4H9, s-C4H9, CH2C6H11 and 1-adamantyl, respectively) together with N3-substitution product 4 (R = CH2C6H5). Bioactivities of the compounds were evaluated. Results show that the analogs 2a, 2c, 2d and 4 are novel antibacterial and cytotoxic agents. The compound 2d exhibits the most potent activity against Branhamella catarrhalis with MIC of 32 μg/mL, while 2c is the most potent cytotoxic against multidrug-resistant small cell lung cancer cell line (H69AR). The analogs 2c and 2d are identified to be novel antimalarials. These novel bioactive analogs are potential lead compounds to be developed as therapeutics. © EuroJournals Publishing, Inc. 2009.