Planta Med 2012; 78 - PD41
DOI: 10.1055/s-0032-1320399

Synthesis and biological activity of some C(9)-hydroxymethyl-5,11-dimethylellipticine derivatives

N Mexia 1, S Michel 2, VPC Rocha 3, CS Meira 3, TS Macedo 3, NC Carvalho 3, FR Nonato 3, MBP Soares 3, AL Skaltsounis 1
  • 1Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, University of Athens, Panepistimiopolis, Athens 15771, Greece
  • 2Laboratoire de Pharmacognosie, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, U.M.R./C.N.R.S. 8638, 4, Avenue de l'Observatoire, 75006 Paris, France
  • 3Laboratory of Tissue Engineering and Immunopharmacology, FIOCRUZ, Salvador, Brazil

The alkaloid ellipticine, first isolated from the Australian Ochrosia elliptica Apocynaceae, exhibits interesting antineoplastic properties. Due to this great antitumoral activity, numerous compounds have been prepared to overcome the lack of selectivity of this series. The moderate cytotoxic activity of some hydroxymethyl derivatives led us to evaluate their antiparasitic properties against commonly drug resistant diseases. So, starting from ellipticine isolated from Strychnos diklangei [1], we have synthesized the 9-formyl derivative and its reduction to 9-hydroxymethylellipticine permitted to achieve new analogues, such as carbamates and acyl esters. These compounds were evaluated for their in vitro activity against L. amazonensis, T. cruzi and P. falciparum and also, their cytotoxicity on splenocytes from BALB/c mice. The results were expressed as IC50 and all the tested derivatives demonstrated good activity against the parasites. Especially carbamates and acyl esters, caused the inhibition of the microbes in lower concentrations, without affecting splenocytes.


References: 1. Michel S. et al. (1980)J. Nat. Prod. 43:2:294–295