title: 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.affiliation: Department of Pharmaceutics, I.T., Banaras Hindu University, Varanasi 221005, India.
authors.forename: S
authors.initials: S
authors.lastname: Shukla
authors.forename: R S
authors.initials: RS
authors.lastname: Srivastava
authors.forename: S K
authors.initials: SK
authors.lastname: Shrivastava
authors.forename: A
authors.initials: A
authors.lastname: Sodhi
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000042:Absorption; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C040756:1,2-naphthoquinone; D004250:DNA Topoisomerases, Type II