Antiprotozoal and Cytotoxic Studies on Some Isocordoin Derivatives

Abstract

Isocordoin (1) and 2′,4′-dihydroxy-3′-(γ,γ-dimethylallyl)-dihydrochalcone (7), chalcones isolated from the root of Lonchocarpus xuul, together with six analogues of 1 were tested in vitro against promastigotes of Leishmania mexicana and epimastigotes of Trypanosoma cruzi. Additionally, cytotoxic studies with MDCK cells were carried out using the MTT method. Among these derivatives, 2′,4′-diacetoxy-3′-(3-methylbut-2-enyl)-chalcone (2) and 2′,4′-dimethoxy-3′-(3-methylbut-2-enyl)-chalcone (3) showed the strongest antiprotozoal activity and lower cytotoxicity in comparison with isocordoin at a concentration in the µM range. Derivative 3 had the strongest trypanocidal activity with IC₅₀ values lower than those of nifurtimox and benznidazole, the common drugs used against these parasites. The selectivity index calculated for 3 (SI 109.3) confirms the selective trypanocidal activity of this metabolite.

Key words

Lonchocarpus xuul - Leguminosae - isocordoin - Leishmania mexicana - Trypanosoma cruzi

References

• 1 Borges-Argáez R, Peña-Rodríguez L M, Waterman P G. Flavonoids from the stem bark of Lonchocarpus xuul.  Phytochemistry. 2000;  54 611-614
• 2 Borges-Argáez R, Peña-Rodríguez L M, Waterman P G. Flavonoids from two Lonchocarpus species of the Yucatan Peninsula.  Phytochemistry. 2002;  60 533-540
• 3 Borges-Argáez R, Poot-Díaz M E, Waterman P G, Peña-Rodríguez L M. Cytotoxic and antiprotozoal activity of flavonoids from Lonchocarpus spp.  Phytomedicine. 2007;  14 530-533
• 4 Puebla-Pérez A M, Herrera-Hernández R A, Villaseñor-García M M, Viveros-Paredes J, Delgado-Saucedo J I, Gallegos-Arreola M P, Borges-Argáez R. Effect of isocordoin in the release of TGF-β1 of mice with L5178Y lymphoma. Río de Janeiro, Brazil; 13th International Congress of Immunology 2007
• 5 Poot-Díaz M E. Actividad biológica de los derivados de isocordoína [thesis]. Mérida, México; Universidad Autónoma de Yucatán 2005
• 6 Goncalves de Lima O, Marini-Bettolo G B, De Mello J F, Delle Monache F, De Barros Coelho J S, De Andrade Lira F D, Fernandes de Alburquerque M M. C‐and O-prenylated chalcones from Cordoa piaca.  Gazz Chim Italia. 1973;  103 771-777
• 7 Delle Monache G, De Méllo J F, Delle Monache F, Marini-Bettolo G B, De Lima G O, De Barros Coelho J S. New prenylated flavonoids of Cordoa piaca (Lonchocarpus sp).  Gazz Chim Italia. 1974;  104 861-865
• 8 Delle Monache F, Goncalves de Lima O, De Méllo J F, Delle Monache G, Marini-Bettolo G B. Chroman-and cromene-chalcones from cordoin and isocordoin.  Gazz Chim Italia. 1973;  103 779-791
• 9 Do Nascimento M C, Mors W B. Chalcones of the root bark of Derris sericea.  Phytochemistry. 1972;  11 3023-3028
• 10 Awouafack M D, Kouam S F, Hussain H, Ngamga D, Tane P, Schulz B, Green I R, Krohn K. Antimicrobial prenylated dihydrochalcones from Eriosema glomerata.  Planta Med. 2008;  74 50-54
• 11 Encarnación-Dimayuga R, Murillo-Alvarez R, Christophersen J I, Chan-Bacab M, Garcia Reiriz M L, Zacchino S. Leishmanicidal, antifungal and cytotoxic activity of triterpenoid glycosides isolated from the sea cucumber Neothyone gibbosa.  Nat Prod Commun. 2006;  1 541-547
• 12 Hocquemiller R, Cortes D, Arango G J, Myint S H, Cavé A. Isolement et synthese de l'espintanol, nouveau monoterpene antiparasitaire.  J Nat Prod. 1991;  54 445-452
• 13 Rahman A, Choudhary M I, Thomsen W J. Bioassay techniques for drug development. Netherlands; Harwood Academic Publisher 2001: 34-35