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Molecules 2013, 18(3), 3356-3378; https://doi.org/10.3390/molecules18033356

Diosgenone Synthesis, Anti-Malarial Activity and QSAR of Analogues of This Natural Product

1
Grupo Malaria, Facultad de Medicina, Universidad de Antioquia, 050010 Medellín, Colombia
2
Programa de Biología, Facultad de Ciencias Básicas, Universidad del Atlántico, 080001 Barranquilla, Colombia
3
Grupo de Química Orgánica de Productos Naturales, Instituto de Química, Universidad de Antioquia, 050010 Medellín, Colombia
4
Instituto de Estructura de la Materia, CSIC, 28006 Madrid, Spain
5
Instituto de Química-Física Rocasolano, CSIC, 28006 Madrid, Spain
*
Author to whom correspondence should be addressed.
Received: 15 January 2013 / Revised: 6 March 2013 / Accepted: 7 March 2013 / Published: 14 March 2013
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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. View Full-Text
Keywords: malaria; natural product; steroid; diosgenone; structural analogue; animal model malaria; natural product; steroid; diosgenone; structural analogue; animal model
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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.

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