Dihydrochalcones and Benzoic Acid Derivatives from Piper dennisii

Abstract

Two new dihydrochalcones (1, 2), as well as eight known compounds, piperaduncin C (3), 2′,6′-dihydroxy-4′-methoxydihydrochalcone (4), 4,2′,6′-trihydroxy-4′-methoxydihydrochalcone (5), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (6), 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (7), 4-hydroxy-3-(3-methyl-2-butenoyl)-5-(3-methyl-2-butenyl)-benzoic acid (8), 2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-1-chromene-6-carboxylic acid (9), and 3-(3′,7′-dimethyl-2′,6′-octadienyl)-4-methoxybenzoic acid (10) were isolated from the leaves of Piper dennisii Trelease (Piperaceae), using a bioassay-guided fractionation to determine their antileishmanial potential. Among them, compound 10 exhibited the best antileishmanial activity (IC₅₀ = 20.8 µM) against axenic amastigote forms of Leishmania amazonensis, with low cytotoxicity on murine macrophages. In the intracellular macrophage-infected model, compound 10 proved to be more active (IC₅₀ = 4.2 µM). The chemical structures of compounds 1–10 were established based on the analysis of the spectroscopic data.

Key words

Piper dennisii - Piperaceae - dihydrochalcones - benzoic acids - antileishmanial activities - cytotoxicity

• References

• 1 Jaramillo MA, Manos PS. Phylogeny and patterns of floral diversity in the genus Piper (Piperaceae). Am J Bot 2001; 88: 706-716
• 2 Cabanillas BJ, Le Lamer AC, Castillo D, Arevalo J, Rojas R, Odonne G, Bourdy G, Moukarzel B, Sauvain M, Fabre N. Caffeic acid esters and lignans from Piper sanguineispicum . J Nat Prod 2010; 73: 1884-1890
• 3 Estevez Y, Castillo D, Tangoa-Pisango M, Arevalo J, Rojas R, Alban J, Deharo E, Bourdy G, Sauvain M. Evaluation of the leishmanicidal activity of plants used by Peruvian Chayahuita ethnic group. J Ethnopharmacol 2007; 114: 254-259
• 4 Odonne G, Bourdy G, Castillo D, Estevez Y, Lancha-Tangoa A, Alban-Castillo J, Deharo E, Rojas R, Stien D, Sauvain M. Taʼtaʼ, Huayani: perception of leishmaniasis and evaluation of medicinal plants used by the Chayahuita in Peru. Part II. J Ethnopharmacol 2009; 126: 149-158
• 5 Valadeau C, Pabon A, Deharo E, Albán-Castillo J, Estevez Y, Lores-Fransis A, Rojas R, Gamboa D, Sauvain M, Castillo D, Geneviève B. Medicinal plants from the Yanesha (Peru): evaluation of the leishmanicidal and antimalarial activity of selected extracts. J Ethnopharmacol 2009; 123: 413-422
• 6 Valadeau C, Alban Castillo J, Sauvain M, Francis Lorese A, Bourdy G. The rainbow hurts my skin: medicinal concepts and plants uses among the Yanesha (Amuesha), an Amazonian Peruvian ethnic group. J Ethnopharmacol 2010; 127: 175-192
• 7 Castillo D, Arevalo J, Herrera F, Ruiz C, Rojas R, Rengifo E, Vaisberg A, Lock O, Lemesre JL, Gornitzka H, Sauvain M. Spirolactone iridoids might be responsible for the antileishmanial activity of a Peruvian traditional remedy made with Himatanthus sucuuba (Apocynaceae). J Ethnopharmacol 2007; 112: 410-414
• 8 Orjala J, Wright AD, Behrends H, Folkers G, Sticher O, Rüegger H, Rali T. Cytotoxic and antibacterial dihydrochalcones from Piper aduncum . J Nat Prod 1994; 57: 18-26
• 9 Orjala J, Erdelmeier CAJ, Wright AD, Rali T, Sticher O. Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and molluscicidal activity from Piper aduncum leaves. Planta Med 1993; 59: 546-551
• 10 Flores N, Jimenez I, Gimenez A, Ruiz G, Gutierrez D, Bourdy G, Bazzocchi L. Benzoic acid derivatives from Piper species and their antiparasitic activity. J Nat Prod 2008; 71: 1538-1543
• 11 Burke B, Nair M. Phenylpropene, benzoic acid and flavonoid derivatives from fruit of Jamaican Piper species. Phytochemistry 1986; 25: 1427-1430
• 12 Hermoso A, Jimenez IA, Mamani ZA, Bazzocchi IL, Pinero JE, Ravelo AG, Valladares B. Antileishmanial activities of dihydrochalcones from Piper elongatum and synthetic related compounds. Structural requirements for activity. Bioorg Med Chem 2003; 11: 3975-3980
• 13 Joshi J, Li XC, Nimrod AC, ElSohly HN, Walker LA, Clark AM. Dihydrochalcones from Piper longicaudatum . Planta Med 2001; 67: 186-188
• 14 Mabry TJ, Sakakibara M, King B. Asebotin and its aglucone from three species of Rhohodendron. Phytochemistry 1975; 14: 1448-1450
• 15 Orjala J, Erdelmeier CAJ, Wright AD, Rali T, Sticher O. Two carotenes and a prenylated benzoic acid derivative from Piper aduncum . Phytochemistry 1993; 34: 813-818
• 16 Moreira DL, Guimaraes EF, Kaplan MAC. A chromene from Piper aduncum . Phytochemistry 1998; 48: 1075-1077
• 17 Baldoqui DC, Kato MJ, Cavalheiro AJ, Da Silva Bolzani V, Young MCM, Furlan M. A chromene and prenylated benzoic acid from Piper aduncum . Phytochemistry 1999; 51: 899-902
• 18 Amaro-Luis JM, Koteich-Khatib S, Carrillo-Rodríguez F, Bahsas A. Myrsicorianol, a new prenylated benzoic acid derivative from Myrsine coriácea . Nat Prod Commun 2008; 3: 323-327
• 19 Parmar V, Jain SC, Bisht KS, Jain R, Taneja P, Jha A, Tyagi OD, Prasad AK, Wengel AJ, Olsen CE, Boll PM. Phytochemistry of genus Piper. Phytochemistry 1997; 46: 591-673
• 20 Flores N, Jimenez I, Gimenez A, Ruiz G, Gutierrez D, Bourdy G, Bazzocchi L. Antiparasitic activity of prenylated benzoic acid derivatives from Piper species. Phytochemistry 2009; 70: 621-627