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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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.