Synthesis, characterization and antiproliferative activity of 1,2-naphthoquinone and its derivatives

Abstract

In the present study substituted 1,2-naphthoquinones were synthesized, purified and characterized by spectroscopic studies (UV, FT-IR, 1H NMR, 13C NMR and elemental analysis). These compounds were evaluated for cytotoxicity against a panel of human cancer cell lines (Hep-G2 for liver sarcoma, MG-63 for osteosarcoma and MCF-7 for human breast cancer). The cells were dosed with these ortho-naphthoquinone derivatives at varying concentrations, and cell viability was measured by a 3-(4,5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) assay with doxorubicin as positive control. Significant anticancer activities were observed in vitro for some members of the series, and compounds 1,2-naphthoquinone 2-thiosemicarbazone (3), 1,2-naphthoquinone-2-semicarbazone (4), 4- amino-1,2-naphthoquinone 2-thiosemicarbazone (7) and 4-amino-1,2-naphthoquinone-2- semicarbazone (8) are active cytotoxic agents against different cancer cell lines with IC50 values in the range of 5.73-17.67 μM. The obtained data suggested that better anticancer activity was linked with introduction of thiosemicarbazone and semicarbazone moiety in 1,2-naphthoquinone ring system. Outcomes of experimentation also reveal that incorporation of amino group in 1,2-naphthoquinone moiety contributes positively for cytotoxic action of compounds. Docking experiments showed a good correlation between their calculated interaction energies with the topoisomerase-II and the observed IC50 values of all these compounds. © Springer Science+Business Media, LLC 2012.