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

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.

• Autores: Pabón Vidal, Adriana Lucía; Escobar Peláez, Gustavo; Vargas Cano, Esteban; Cruz Cañas, Víctor; Notario Bueno, Rafael; Blair Trujillo, Silvia
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2013
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/23685
• Acceso en línea: http://hdl.handle.net/10495/23685
• Palabra clave: Productos naturales; Natural products; Malaria; Steroids; Esteroides; Animal model; Modelos animales; http://aims.fao.org/aos/agrovoc/c_34312; http://aims.fao.org/aos/agrovoc/c_7407; http://aims.fao.org/aos/agrovoc/c_34782
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/