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, ¹³ C 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, 1,2-naphthoquinone-2-semicarbazone, 4-amino-1,2-naphthoquinone 2-thiosemicarbazone and 4-amino-1,2-naphthoquinone-2-semicarbazone 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.

• Authors: S Shukla, R S Srivastava, S K Shrivastava, A Sodhi, Pankaj Kumar
• Journal: Applied biochemistry and biotechnology (Appl Biochem Biotechnol) Vol. 167 Issue 5 Pg. 1430-45 (Jul 2012) ISSN: 1559-0291 [Electronic] United States
• PMID: 22258648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Naphthoquinones
• 1,2-naphthoquinone
• DNA Topoisomerases, Type II

Topics

• Absorption
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chemistry Techniques, Synthetic
• DNA Topoisomerases, Type II (chemistry, metabolism)
• Humans
• Inhibitory Concentration 50
• Models, Molecular
• Naphthoquinones (chemical synthesis, chemistry, metabolism, pharmacology)