A Highly Active Triterpene Derivative Capable of Biofilm Damage to Control Cryptococcus spp.

Abstract

Cryptococcus neoformans is an encapsulated yeast responsible for more than 180,000 deaths per year. The standard therapeutic approach against cryptococcosis is a combination of amphotericin B with flucytosine. In countries where cryptococcosis is most prevalent, 5-fluorocytosine is rarely available, and amphotericin B requires intravenous administration. C. neoformans biofilm formation is related to increased drug resistance, which is an important outcome for hospitalized patients. Here, we describe new molecules with anti-cryptococcal activity. A collection of 66 semisynthetic derivatives of ursolic acid and betulinic acid was tested against mature biofilms of C. neoformans at 25 µM. Out of these, eight derivatives including terpenes, benzazoles, flavonoids, and quinolines were able to cause damage and eradicate mature biofilms. Four terpene compounds demonstrated significative growth inhibition of C. neoformans. Our study identified a pentacyclic triterpenoid derived from betulinic acid (LAFIS13) as a potential drug for anti-cryptococcal treatment. This compound appears to be highly active with low toxicity at minimal inhibitory concentration and capable of biofilm eradication.

Bioactive triterpenoids from Solanum torvum fruits with antifungal, resistance modulatory and anti-biofilm formation activities against fluconazole-resistant candida albicans strains

“…Some of these compounds however, have been known to exert this effect in some bacteria. Betulinic acid ( 1 ) significantly decreased biofilm formation in Pseudomonas aeruginosa at sub-MIC levels and have also been shown to inhibit biofilm formation in Cryptococcus neoformans [ 58 , 59 ] whiles oleanolic acid ( 4 ) has demonstrated anti-biofilm activity across a wide range of Gram-positive and Gram-negative bacteria [ 60 , 61 ]. The anti-biofilm activity of the isolated compounds may contribute in part to the efficacy of S .…”