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

Molecules

Adriana Pabón¹  Gustavo Escobar²  Esteban Vargas²  Vໜtor Cruz³  Rafael Notario⁴  Silvia Blair¹ 

[1] Grupo Malaria, Facultad de Medicina, Universidad de Antioquia, 050010 Medellín, Colombia; E-Mails:;Grupo de Química Orgánica de Productos Naturales, Instituto de Química, Universidad de Antioquia, 050010 Medellín, Colombia; E-Mails:;Instituto de Estructura de la Materia, CSIC, 28006 Madrid, Spain; E-Mail:;Instituto de Química-Física Rocasolano, CSIC, 28006 Madrid, Spain; E-Mail:

关键词: malaria;    natural product;    steroid;    diosgenone;    structural analogue;    animal model;   

DOI  :  10.3390/molecules18033356

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.