SYNTHESIS AND CYTOTOXIC EVALUATION OF SUBSTITUTED SULFONYL-N-HYDROXYGUANIDINE DERIVATIVES AS POTENTIAL ANTITUMOR AGENTS

A series of sulfonyl-N-hydroxyguanidine derivatives was designed and s ynthesized for cytotoxic evaluation as potential anticancer agents on the basis of the lead compound LY-181984. Replacement of the ureido mo iety of the lead compound with hydroxyguanidine provided a stable cyto toxic agent. The conformation of sulfonyl-N-hydroxyguanidine derivativ es, such as enyl)-N'-[(benzo[2,1,3]thiadiazol-4-yl)sulfonyl]-N ''-hydr oxyguanidine (4g), investigated utilizing HMBC NMR, theoretical calcul ations, and X-ray crystallography, indicated stacking of the two aroma tic rings. The derivatives were evaluated for in vitro cytoxicity agai nst five human tumor cell lines, including HepG2, TSGH 8302, COLO 205, KB, and MOLT-4. The cytotoxic activities of the derived compounds aga inst the human tumor cell lines were equal to or greater than that of the lead compound. [3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl]-N ''-hydroxyguanidine (4n) and loro-4-(2-chloro-4-nitrophenoxy)phenyl]su lfonyl]-N ''-hydroxyguanidine (4o) exhibited the greatest growth inhib ition of solid tumor cell lines. Compound 4o was found to possess anti tumor activity against murine K1735/M2 melanoma xenografts.