Alkaloids from Tabernaemontana divaricata combined with fluconazole to overcome fluconazole resistance in Candida albicans.

ABSTRACT

Nineteen indole alkaloids including eleven new ones, taberdines A-K (1-11), were isolated from Tabernaemontana divaricata. Their structures were assigned by MS, NMR, single crystal X-ray diffractions, and ECD analyses. Alkaloid 1 is an aspidosperma-type monoterpenoid indole alkaloid and possesses a rearranged pyrrolidine moiety due to C-3 degradation, and 4 has a rare 1,3-oxazolidine moiety within iboga-type alkaloids. Alkaloids 2, 4, 6, and 11-19 combined with 5 µg/mL fluconazole exhibited significant activity to reverse fluconazole resistance in Candida albicans strains while no one used alone showed any activities against the resistant strain.