Microwave-Assisted Semisynthesis and Leishmanicidal Activity of Some Phenolic Constituents from Lichens
Grover Castañeta,
Rodrigo Villagomez,
Efrain Salamanca,
Pamela Canaviri-Paz,
José A. Bravo,
José L. Vila,
Daniela Bárcenas-Pérez,
José Cheel,
Beatriz Sepúlveda,
Alberto Giménez,
Carlos Areche
Affiliations
Grover Castañeta
Instituto de Investigaciones Químicas IIQ, Universidad Mayor de San Andrés UMSA, Av. Villazón N° 1995, Box 303, La Paz 0201-0220, Bolivia
Rodrigo Villagomez
Instituto de Investigaciones Químicas IIQ, Universidad Mayor de San Andrés UMSA, Av. Villazón N° 1995, Box 303, La Paz 0201-0220, Bolivia
Efrain Salamanca
Instituto de Investigaciones Fármaco Bioquímicas, Área de Química Farmacéutica, Facultad de Ciencias Farmacéuticas y Bioquímicas, Universidad Mayor de San Andrés, Av. Saavedra N° 2224, Miraflores, Box 303, La Paz 0201-0220, Bolivia
Pamela Canaviri-Paz
Department of Food Technology, Engineering and Nutrition, Faculty of Engineering, Lund University, Box 117, SE-221 00 Lund, Sweden
José A. Bravo
Instituto de Investigaciones Químicas IIQ, Universidad Mayor de San Andrés UMSA, Av. Villazón N° 1995, Box 303, La Paz 0201-0220, Bolivia
José L. Vila
Instituto de Investigaciones Químicas IIQ, Universidad Mayor de San Andrés UMSA, Av. Villazón N° 1995, Box 303, La Paz 0201-0220, Bolivia
Daniela Bárcenas-Pérez
Laboratory of Algal Biotechnology-Centre ALGATECH, Institute of Microbiology of the Czech Academy of Sciences, Opatovicky Mlyn, 37981 Trebon, Czech Republic
José Cheel
Laboratory of Algal Biotechnology-Centre ALGATECH, Institute of Microbiology of the Czech Academy of Sciences, Opatovicky Mlyn, 37981 Trebon, Czech Republic
Beatriz Sepúlveda
Departamento de Ciencias Químicas, Campus Viña del Mar, Universidad Andres Bello, Quillota 980, Viña del Mar 2520000, Chile
Alberto Giménez
Instituto de Investigaciones Fármaco Bioquímicas, Área de Química Farmacéutica, Facultad de Ciencias Farmacéuticas y Bioquímicas, Universidad Mayor de San Andrés, Av. Saavedra N° 2224, Miraflores, Box 303, La Paz 0201-0220, Bolivia
Carlos Areche
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Box 653, Las Palmeras 3425, Ñuñoa, Santiago 8320000, Chile
Leishmaniasis is considered one of the most untreated tropical diseases in the world. In this study, we investigated the in vitro leishmanicidal activity and cytotoxicity of various isolated lichen substances, including atranorin (1), usnic acid (2), gyrophoric acid (3), salazinic acid (4), galbinic acid (5), and parietin (6), and some semi-synthetic imine derivatives of usnic acid (7, 8, 9) and atranorin (10, 11, 12, 13). Imine condensation reactions with hydrazine and several amines were assisted by microwave heating, an efficient and eco-friendly energy source. The most interesting result was obtained for compound 2, which has high leishmanicidal activity but also high cytotoxicity. This cytotoxicity was mitigated in its derivative, 9, with better selectivity and high antileishmanic activity. This result may indicate that the usnic acid derivative (9) obtained using condensation with two cyclohexylamine groups is a promising lead compound for the discovery of new semisynthetic antiparasitic drugs.
