Bicyclic isothioureas for conjugation with tubulin targeted anticancer agents

Two bicyclic annulated isothiourea derivatives were synthesized using as a key stage either the reaction of isothiocyanate halide with sodium sulfide or cyclization of unsaturated thiourea in the presence of bromine. X-ray molecular structure of N-[(3aSR,7aRS,Z)-hexahydro-1,3-benzothiazol-2(3H)-ylidene]glycine was determined. The conjugate of colchicine with [(3aR,5S,6aS)-2-(tert-butylamino)-3a,5,6,6a-tetrahydro-4H-cyclopenta[d]thiazol-5-yl]methanol obtained demonstrated pronounced cytotoxic effect on cancer cells.