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

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

Received: 15 January 2013; in revised form: 6 March 2013 / Accepted: 7 March 2013 / Published: 14 March 2013
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.

AMA 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(3):3356-3378.

Chicago/Turabian Style

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.

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