Synthesis and anticancer activity evaluation of naphthalene-substituted triazole spirodienones

Abstract

Building on our previous work that discovered 1,2,4-triazole-spirodienone as a promising pharmacophore for anticancer activity, we have further diversified 1,2,4-triazole- spirodienone derivatives and synthesized a series of novel naphthalene-substituted triazole spirodienones to explore their antineoplastic activity. Of these, compound 6a possesses remarkable in vitro cytotoxic activity by arresting cell cycle and inducing apoptosis in MDA-MB-231 cells. Subsequently, acute toxicity assay showed that 6a at 20 mg/kg has no apparent toxicity to the major organ in mice. In addition, compound 6ain vivo suppressed breast cancer 4T1 tumor growth. Taken together, these results indicate that compound 6a may be a potential anticancer agent for further development.

Keywords: 4T1 breast tumor; Anti-proliferation; Cytotoxicity; MDA-MB-231; Naphthalene-substituted triazole spirodienones.