Synthesis and in vitro antiproliferative effect of isomeric analogs of cyclobrassinin phytoalexin possessing the 1,3-thiazino[5,6-b]indole-4-one skeleton

Isomeric analogs of cyclobrassinin phytoalexin possessing the 1,3-thiazino[5,6-b]indole-4-one skeleton have been prepared. Starting from 1H-indole-2-carbonyl isothiocyanate, N-aryl-N'-(indole-2-carbonyl)-substituted thiourea or the corresponding S-aryl-N-(indole-2-carbonyl)dithiocarbamate intermediates were prepared and then transformed by ring closure via Hugerschoff reaction with phenyltrimethylammonium tribromide. Attempted synthesis of N'-(indole-2-carbonyl)-N-(3,4,5-trimethoxyphenyl)thiourea unexpectedly delivered the 2-(indole-2-carbonylamino)-5,6,7-trimethoxy-benzothiazole ring system. The structures of the new ring systems were determined by means of IR and NMR spectroscopy. The new derivatives synthesized exert moderate in vitro antiproliferative effects on a panel of adherent human cell lines (HeLa, A2780, A431 and MCF7). [GRAPHICS]