2-hydroxy-8-methyl-1,7-dioxaspiro[5.5]undec-3-en-5-one: a Natural-Product-Inspired Spiroketal with in vivo Efficacy in Mouse Model of Melanoma

We have synthesised and identified a new promising antitumor agent with in vivo activity on a murine melanoma model. Compound 1 showed potent dose-dependent antitumor efficacy in syngenic C57Black mice murine model of melanoma, suppressing the tumor growth by an average of 90% at a dose of 5 mg/kg by intra-peritoneum administration at alternate days for 15 days. It also displayed high antitumor activity in the B16 cells in vitro with nanomolar EC50 value. In addition to the proapoptotic and telomerase inhibition activity, compound 1 has shown to inhibit cell migration and to strongly reduce the HIF1? expression, that is considered a regulator of multiple cellular functions related to the progression from primary to metastatic cancer disease. Therefore, although the full mechanism/s of action of this molecule has yet to be completely elucidated, spiroketal 1 is a promising antitumor drug candidate for the clinical treatment of melanoma and various cancers.