Anti-HIV activity of Δ18-oleane triterpenoids from Cassine xylocarpa
The species of the Celastraceae have a long history in traditional medicine, and they produce an extraordinary variety of bioactive metabolites, including pentaciclic triterpenoids. Thus, a diversity of oleane-type triterpenoids have been isolated from this family, mainly those corresponding to the Δ12-oleane skeleton, however, only a few examples of Δ18-oleane-type have been reported.
The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). Although antiretroviral therapy (ART) is able to stop the progression of the disease, drug toxicity and viral resistance are important limitations. Therefore, an unprecedented effort is being performed to find new anti-HIV drugs with acceptable toxicity, good resistance profiles and novel mechanisms of action. Thus, bevirimat, a derivative of betulinic acid represents a unique first-in-class of anti-HIV compounds known as maturation inhibitors (MIs), which has succeeded in phase IIb clinical trials. In addition, moronic acid, a Δ18-oleane triterpene, also exhibits promising anti-HIV activity as a lead compound with an EC50 of 0.1µg/mL and a good therapeutic index (TI >186) relative to its cytotoxicity. As a part of our research for bioactive compounds from Celastraceae species, herein we report the isolation of eleven new Δ18-oleane triterpenes, along with two known ones, from the stem of Cassine xylocarpa Vent.. Their structures were determined by spectroscopic methods, including 1D and 2D NMR techniques. The compounds were tested for their activity as inhibitors of HIV replication. Ten of the compounds showed significant inhibitory effects, ranging from 66 to 99% at a concentration of 10µM.
Acknowledgement: We are indebted to the Agencia Canaria de Investigación, Innovación y Sociedad de la Información (C200801000049) project for financial support.Osorio AA. thanks to MAEC-AECID for the fellowship.
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