Importance of the C9 absolute configuration for the antifungal activity of natural and semisynthetic sesquiterpenes

DERITA, M.; DI LIBERTO, M.; ZACCHINO, S.

Science and Technology against Microbial Pathogens. Research, Development and Evaluation

World Scientific Publishing Co. Pte. Ltd

Año: 2011; p. 372 - 376

 Since the early 1980s, fungal infections have emerged as major causes of morbi-mortality, mainly among immunocompromised patients. The majority of deaths were associated with species of Candida, Aspergillus and Cryptococcus.[1] Instead, dermatophytes such as Trichophyton and Microsporum spp. produce superficial infections (tineas) which are usually not threatening but dramatically diminish the quality of life of human beings.[2] Although it appears to be an array of antifungal agents (polyenes, azoles, allylamines and the recent echinocandins) there are, in fact, few therapeutic options. Decreased susceptibilities of yeasts to the currently available antifungal agents[3] added to the increase in the number of reported cases of resistance,[4] have led to a general consensus that new efforts for detecting novel antifungal entities remain a priority. In this context, the study of plants with history of ethnopharmacological use for ailments related to fungal infections, can serve two goals: validation of the use of traditional medicines and finding new leads.[5] The genus Polygonum (Polygonaceae) is represented in Argentina by 21 species which are divided into five sections: Amblygonum, Echinocaulon, Tiniaria, Polygonum and Persicaria. Most of these species are reported to have interesting biological activities.[6] In a previous work we reported the isolation of two sesquiterpene dialdehydes [polygodial (1) and isopolygodial (2)] and a related alcohol [drimenol (3)] from Polygonum acuminatum Kunth, a species belonging to Persicaria section.[7] In this paper we describe the obtainment of isodrimenol (4) by semisynthetic means, and the evaluation of the antifungal activities of the four compounds in order to establish the importance of C9 absolute configuration of these sesquiterpene-drimanes for its antifungal activities.