Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa and In Depth Investigation of Their in vitro and in vivo Antifungal Activities

Abstract

As a part of a broad screening of antifungal agents from plant origin, crude extracts from Panamanian plants having related types of constituents displayed significant activities in an agar overlay thin layer chromatography assay against a susceptible strain of Candida albicans. These were the methanolic extract of the leaves of Schefflera systyla and Odontadenia puncticulosa and of the stems of Conostegia speciosa, that are species not previously investigated from a phytochemical viewpoint. For all plants, high-performance liquid chromatography (HPLC) antifungal activity based profiling allowed the rapid localization of antifungal agents that were further obtained by targeted isolation procedure by semi-preparative HPLC or medium pressure liquid chromatography (MPLC) after LC gradient transfer. Different hederagenin saponins and one aglycone were found to be responsible for the antifungal activities of the extracts. Alpha-hederin was the antifungal of S. systyla, pulsatilla saponin D and 3β-O-[β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranosylhederagenin of O. puncticulosa and arjunolic acid of C. speciosa. Their minimal inhibitory concentration (MIC) against planktonic and biofilm cells of C. albicans were determined. Alpha-hederin was the most potent compound with a MIC of 4 µg mL -1 . Structurally related compounds (hederagenin, medicagenic acid 3-O-β-D-glucopyranoside and medicagenic acid) were used as standards and tested for comparison purposes. In order to better estimate the potential of these triterpenoids as antifungal agents, their cytological effects on C. albicans were determined by transmission electron microscopy (TEM) and the in vivo activity of alpha-hederin, medicagenic acid 3-O-β-D-glucopyranoside and medicagenic acid was evaluated for the first time in the Galleria mellonella larvae model. Keywords: triterpenoids, microfractionation, antifungal, Candida species, Galleria mellonella IntroductionFungal infections have recently increased worldwide and cause high morbidity and mortality rates among different groups of human patients. 1 The development of drug resistance in fungal pathogens compromises the efficacy of the limited number of therapeutic agents. 2The main fungal opportunistic human pathogens are Candida spp., and among them, the most common species is Candida albicans. 3 In the USA, Candida species are the fourth cause of nosocomial bloodstream infections. 4,5 Over 400,000 candidiasis infections are declared per year worldwide. 6 Moreover, Candida species display a tendency Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa J. Braz. Chem. Soc. 444 to grow as biofilms on implanted medical devices such as a central venous catheter. 7 Biofilm cells exhibit up to a 1,000-fold increase in resistance as compared to their planktonic counterparts 8 which may contribute to therapeutic failures. 9 These facts make urgent the need to identify new chemical entities that may lead to the disc...

Identification of Antifungal Compounds from the Root Bark of Cordia anisophylla J.S. Mill.

“…is a small tree that grows from the center of Panama to the border of Columbia. In our continuous search for antifungal compounds of natural origin, [6][7][8][9] the dichloromethane (DCM) extract of the root bark of C. anisophylla demonstrated significant antifungal activity in a primary bioautography screen against C. albicans, one of the most opportunistic fungi that infects humans. 10 C. albicans can colonize human skin and mucosal surfaces, causing a wide spectrum of diseases ranging from benign mucosal infections such as oral thrush to fatal disseminated candidiasis.…”