Synthesis of isothiosemicarbazones of potential antitumoral activity through a multicomponent reaction involving allylic bromides, carbonyl compounds and thiosemicarbazide

A convenient route for the synthesis of isothiosemicarbazones and 2-hydrazono-1,3-thiazin-4-ones through a multicomponent reaction featuring allylic bromides, carbonyl compounds and thiosemicarbazides is described. The transformations proceed under mild and environmentally benign conditions with high yields and stereoselectivity. All novel compounds were obtained in high purity without the need for chromatography stages. Different functional groups are well tolerated, including halogen, alkoxy, nitro and unsaturated groups. This simple protocol offers straightforward access to a wide range of highly functionalized substances with pharmacologically privileged structures. All compounds were fully characterized and the structural assignment of key products was unequivocally confirmed by X-ray diffraction analysis. Selected isothiosemicarbazones were screened against a triple-negative breast cancer cell line and some compounds were shown to reduce the number of live tumoral cells (41-54%). (C) 2020 Elsevier Ltd. All rights reserved.