A new dimeric monoterpene indole alkaloid from the stem bark of Pleiocarpa mutica Benth. (Apocynaceae)

In the search for antiplasmodial molecules from plants used in traditional African medicine, the study of the alkaloidic extract of the stem bark of Pleiocarpa mutica Benth. (Apocynaceae), collected in Gabon, was carried out by a structure-driven HPLC-ESI-Q/TOF dereplication strategy, using the “molecular network” approach [1]. This strategy led to the rapid detection of over twenty known compounds [2], several of which were isolated for means of biological evaluation, such as the heterosidic monomer vincosamide (1) and the aspidofractine/eburnamine dimer pleiomutine (2). Analysis of the alkaloidic extract network also revealed the presence of a new and unusual bisindole alkaloid of the aspidofractine series, pleiokomenine (3). Spectral data (1D, 2D NMR and MS) of purified 3 evidenced a homodimeric aspidofractine skeleton, with an original methylene linker. Pleiokomenine (3) showed an interesting activity against Plasmodium falciparum (FcB1 strain), with an IC₅₀ of 3.7µM. Structural elucidation of several analogues is in progress.

Acknowledgements: We are grateful to Jean-Christophe Jullian and Camille Dejean for NMR assistance.

Keywords: Apocynaceae, aspidofractine, HPLC-MS/MS, Molecular networking, Plasmodium falciparum, Pleiocarpa mutica.

References:

[1] Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD, Bruns N, Glukhov E, Wodtke A, de Felicio R, Fenner A, Wong WR, Linington RG, Zhang L, Debonsi HM, Gerwick WH, Dorrestein PC. Molecular networking as a dereplication strategy. J Nat Prod 2013; 76: 1686 – 1699

[2] Thomas DW, Achenbach H, Bieman K. A new dimeric indole alkaloid from Pleiocarpa mutica Benth. J Am Chem Soc 1966; 88: 1537 – 1544