Anti-Candida Cassane-Type Diterpenoids from the Root Bark of Swartzia simplex

Abstract

A dichloromethane extract of the roots from the Panamanian plant Swartzia simplex exhibited a strong antifungal activity in a bioautography assay against a genetically modified hypersusceptible strain of Candida albicans. At-line HPLC activity based profiling of the crude extract enabled a precise localization of the antifungal compounds, and dereplication by UHPLC-HRESIMS indicated the presence of potentially new metabolites. Transposition of the HPLC reversed-phase analytical conditions to medium-pressure liquid chromatography (MPLC) allowed an efficient isolation of the major constituents. Minor compounds of interest were isolated from the MPLC fractions using semipreparative HPLC. Using this strategy, 14 diterpenes (1-14) were isolated, with seven (5-10, 14) being new antifungal natural products. The new structures were elucidated using NMR spectroscopy and HRESIMS analysis. The absolute configurations of some of the compounds were elucidated by electronic circular dichroism spectroscopy. The antifungal properties of these compounds were evaluated as their minimum inhibitory concentrations in a dilution assay against both hypersusceptible and wild-type strains of C. albicans and by assessment of their antibiofilm activities. The potential cytological effects on the ultrastructure of C. albicans of the antifungal compounds isolated were evaluated on thin sections by transmission electron microscopy.

Enantioconvergent Biocatalytic Redox Isomerization

“…Furthermore, a base‐mediated ring contraction gave access to the corresponding γ‐lactone ( S )‐ 7 with complete conservation of optical activity. Since both 6 and 7 represent core scaffolds in numerous complex natural products such as echinolactone B ( 8 ) and simplexene B ( 9 ), a focus in our upcoming studies lies on the elucidation of the extended scope of the hydroxyenone isomerases on this particular substrate family.…”

Diterpenoids of terrestrial origin

“…Other cassanes have been isolated from Erythrophleum suaveolens 132 and Swartzia simplex. 133 The activation by epigenetic mining of a silent biosynthetic pathway in the fungus Calcarisporium arbuscula led to the isolation 18 of arbusculic acid A 44. A new phytoalexin phytocassane F 45 has been identied 134 in rice leaves that had been subjected to UV radiation.…”

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.…”