Evaluation of synergistic effect of kaurenoic acid derivatives with fluconazole a gainst strains of fluconazole-resistant Candida parapsilosis

Abstract

Candida species are the fourth most common cause of nosocomial bloodstream infections in the United States and the fifth to tenth most common causative pathogen in European studies Although C. albicans remains the most common fungal isolate recovered from blood, recent reports indicate a trend towards an increasing prevalence of infections caused by species of Candida other than C. albicans which are associated with a highly mortality rate. Furthermore, antifungal drug resistance (i.e. resistance to azole compounds) is a prominent feature in the management of invasive mycoses, and its epidemiological characteristics continue to evolve. This scenario leads to seek for new candidates for antifungal drugs able to overcome the resistance issues of Candida species. Kaurenoic acid (KA) or ent-kaur-16-en-19-oic acid is a tetracyclic diterpene present in several plants known to exert several pharmacological activities such cytotoxic actions and antimicrobial in vitro. The aim of current study was evaluate the potential antifungal of the natural diterpenoids kauren-19-oic acid (KA), 14-hydroxy-kaurane (1) and xylopic acid (2), and semi-synthetic derivatives of KA (3-5) towards Candida parapsilosis. Six combinations formed by different diterpenoids kauren-19-oic acid (KA), compounds (1-5), were tested using varied fluconazole concentration. We concluded that the compound 4 (16 -methoxy-( )-kauran-19-oic methylester) when combined with fluconazole, show activity against strains of C. parapsilosis resistant to fluconazole.