Synthesis, cytotoxic evaluation, docking and in silico pharmacokinetic prediction of 4-arylideneamino/cycloalkylidineamino 1, 2-naphthoquinone thiosemicarbazones.

In an attempt to develop potent anticancer agents, a series of 4-arylideneamino/cycloalkylidineamino-1, 2-naphthoquinone thiosemicarbazones were synthesized and characterized using FT-IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis. The compounds were screened for antiproliferative activity against three human cancer cell lines (Hep-G2, MG-63 and MCF-7) using the MTT assay. Significant anticancer activity was observed for several members of the series. The compounds 4-(3, 4, 5-trimethoxybenzylidene amino) 1, 2-naphthoquinone-2-thiosemicarbazone (TS10) and 4-(4-hydroxy-3-methoxy benzylideneamino) 1, 2-naphthoquinone-2-thiosemicarbazone (TS13) were active cytotoxic agents in all three cancer cell lines, with IC50 values in the range of 3.5-6.4 µM. Further evaluation of some of these potent cytotoxic compounds demonstrated their good safety profile in a normal cell line (MCF-12A). Docking experiments showed a good correlation between the predicted glide scores and the IC50 values of these compounds. In silico ADME studies revealed that these compounds can be used for second generation development.