1,2,3-triazole-, arylamino- and thio-substituted 1,4-naphthoquinones: potent antitumor activity, electrochemical aspects, and bioisosteric replacement of C-ring-modified lapachones

Abstract

1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 μM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.

Keywords: 1,2,3-Triazoles; 1,4-Naphthoquinone; Cancer; Click chemistry; Lapachol.