Antiplasmodial and cytotoxic activities of synthetic alkaloids

M. Haddad; E. Sobarzo-Sánchez; S. Maurel; A. Valentin; J. Quetin-Leclercq

doi:10.1055/s-0028-1084789

Planta Medica, Inhaltsverzeichnis

Antiplasmodial and cytotoxic activities of synthetic alkaloids

M Haddad ¹^,³, E Sobarzo-Sánchez ², S Maurel ³, A Valentin ³, J Quetin-Leclercq ¹

¹Laboratoire de Pharmacognosie, Unité d'Analyse Chimique et Physico-Chimique des Médicaments, Université Catholique de Louvain, UCL 72.30-CHAM, Av. E. Mounier 72, 1200 Bruxelles, Belgium
²Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain
³Laboratoire Pharmacochimie des Substances Naturelles et Pharmacophores Redox, UMR 152 IRD, Université Toulouse 3 Paul Sabatier, Faculté des Sciences Pharmaceutiques, Toulouse

Abstract

The number of aporphinoid compounds isolated from plants or obtained by total synthesis is rapidly growing. Numerous molecules in this family display interesting cytotoxic activities against tumor cell lines in vitro and hints of anticancer activities in vivo have been reported in some cases [1]. Some aporphine alkaloids exhibited potential anticancer activity [2,3] and some cytotoxic compounds were found to be potent inhibitors of topoisomerase II [4,5] or to be antiparasitic against Leishmania donovani and Plasmodium falciparum [6].

Since only a few studies concerning the biological properties of synthetic aporphine derivatives were carried out, we evaluated in this study the in vitro activity of 8 synthetic isoquinoline alkaloids against 4 cancer cell lines including HeLa, HL-60, Mel-43 and J-774 cells and against the non-cancer cell line WI-38. Results showed that these compounds exhibited cytotoxic and selective effect towards different cell lines. Moreover, since this type of compounds may possess antiparasitic properties, we decided to evaluate the antiplasmodial activity of these eight synthetic derivatives. One compound was found to exhibit the stronger activity (IC ₅₀=1.45µM). These pharmacological results were compared with their electronic properties by the density-functional theory method and provided a new insight for the cytotoxic and antimalarial activities of natural products.

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3. Harrigan, G.G. et al. (1994)J. Nat. Prod. 57:68.

4. Woo, S.H. et al. (1999a) Biochem. Pharmacol. 57:1141.

5. Woo, S.H. et al. (1999b) Biochem. Pharmacol. 54:467.

6. Camacho, M.R. et al. (2000) Planta Med. 478.