Mavacurane-aspidospermane bisindole alkaloids from Hunteria zeylanica: structural elucidation and revision, bioinspired semisynthesis and cytotoxicity

Abstract

Eight mavacurane-aspidospermane bisindole alkaloids, including five undescribed compounds hunzeylmanes A-E (1-5) and their biosynthetic precursors (9, 10a, and 11a), were isolated from the leaves of Hunteria zeylanica. Their structures including absolute configurations were determined by comprehensive spectroscopic analyses and quantum chemical computational methods. The observation of significant NMR data discrepancies between three alkaloids (7a, 8a, and 10a) and their quaternary ammonium salts (7b, 8b, and 10b) prompted a structural revision of the originally reported 16-epi-pleiomutinine. Bioinspired semisynthesis of compounds 2, 3, 6, and 8a was achieved from isolated precursors via key three-component Povarov or Vilsmeier-Haack reactions. The cytotoxicity of these bisindole alkaloids against four cancer cell lines was evaluated, with compound 1 exhibited marked antiproliferative activities, inducing apoptosis and G0/G1 cell cycle arrest.

Keywords: Apocynaceae; Bioinspired semisynthesis; Bisindole alkaloids; Cytotoxicity; Hunteria zeylanica; Structural revision.