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Diosgenone Synthesis, Anti-Malarial Activity and QSAR of Analogues of This Natural Product
Grupo Malaria, Facultad de Medicina, Universidad de Antioquia, 050010 Medellín, Colombia
Programa de Biología, Facultad de Ciencias Básicas, Universidad del Atlántico, 080001 Barranquilla, Colombia
Grupo de Química Orgánica de Productos Naturales, Instituto de Química, Universidad de Antioquia, 050010 Medellín, Colombia
Instituto de Estructura de la Materia, CSIC, 28006 Madrid, Spain
Instituto de Química-Física Rocasolano, CSIC, 28006 Madrid, Spain
* Author to whom correspondence should be addressed.
Received: 15 January 2013; in revised form: 6 March 2013 / Accepted: 7 March 2013 / Published: 14 March 2013
Abstract: Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 μM vs. 10.1 μM, 2.9 μM and 11.3 μM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.
Keywords: malaria; natural product; steroid; diosgenone; structural analogue; animal model
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MDPI and ACS Style
Pabón, A.; Escobar, G.; Vargas, E.; Cruz, V.; Notario, R.; Blair, S.; Echeverri, F. Diosgenone Synthesis, Anti-Malarial Activity and QSAR of Analogues of This Natural Product. Molecules 2013, 18, 3356-3378.
Pabón A, Escobar G, Vargas E, Cruz V, Notario R, Blair S, Echeverri F. Diosgenone Synthesis, Anti-Malarial Activity and QSAR of Analogues of This Natural Product. Molecules. 2013; 18(3):3356-3378.
Pabón, Adriana; Escobar, Gustavo; Vargas, Esteban; Cruz, Víctor; Notario, Rafael; Blair, Silvia; Echeverri, Fernando. 2013. "Diosgenone Synthesis, Anti-Malarial Activity and QSAR of Analogues of This Natural Product." Molecules 18, no. 3: 3356-3378.