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

Abstract A novel series of twenty 3-thiocyanato-1 H -indoles, carrying diversification at positions N-1, C-2 and C-5 of the heterocyclic core, were synthesized; their antiproliferative activity against four 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 be essentially inactive, whereas several of their congener 3-thiocyanato-1 H -indoles displayed good to excellent levels of potency (IC 50  ≤ 6 μM), while being non-hemolytic. N -Phenyl-3-thiocyanato-1 H -indole and 1-methyl-2-(4-chlorophenyl)-3-thiocyanato-1 H -indole showed good to high potency against all the cell lines. On the other side, the N -(4-chlorophenyl)-, 2-(4-chlorophenyl)- and 2-phenyl- 3-thiocyanato-1 H -indole derivatives were slightly less active against the test cell lines. Overall, these results suggest that the indole-3-thiocyanate motif can be suitably decorated to afford highly cytotoxic compounds and that the substituted indole can be employed as a useful scaffold toward more potent compounds.