Synthesis and preliminary evaluation of 3-thiocyanato-1H-indoles as potential anticancer agents

FORTES, M. P.; DA SILVA, P. B. N.; DA SILVA, T. G.; KAUFMAN, T. S.; MILITAO, G. C. G.; SILVEIRA, C. C.

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Paris; Año: 2016 vol. 118 p. 21 - 26

0223-5234

A novelseries of twenty 3-thiocyanato-1H-indoles,carrying diversification at positions N-1, C-2 and C-5 of theheterocyclic core, were synthesized; their antiproliferative activity againstfour human cancer cell lines (HL60, HEP-2, NCI-H292 and MCF-7) was evaluated,employing doxorubicin as positive control. Indole, N-methylindole and 2-(4-chlorophenyl)-N-methylindole demonstrated to beessentially inactive, whereas several of their congener 3-thiocyanato-1H-indoles displayed good to excellent levelsof potency (IC50 < 6 uM),while being non-hemolytic. N-Phenyl-3-thiocyanato-1H-indole and 1-methyl-2-(4-chlorophenyl)-3-thiocyanato-1H-indole showed good to high potency againstall the cell lines. On the other side, the N-(4-chlorophenyl)-, 2-(4- chlorophenyl)-and 2-phenyl- 3-thiocyanato-1H-indolederivatives were slightly less active against the test cell lines. Overall,these results suggest that the indole-3-thiocyanate motif can be suitablydecorated to afford highly cytotoxic compounds and that the substituted indolecan be employed as a useful scaffold toward more potent compounds.