Antileishmanial Carbasugars from Geosmithia langdonii

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Mycology

Background:

• Filamentous fungi are a rich source of structurally diverse secondary metabolites.
• Geosmithia langdonii, isolated from cotton textiles, represents an underexplored microbial source for novel compounds.
• Leishmaniasis remains a significant global health concern, necessitating the discovery of new therapeutic agents.

Purpose of the Study:

• To isolate and characterize new carbasugar-type metabolites from Geosmithia langdonii.
• To evaluate the antileishmanial activity of the isolated compounds.
• To determine the absolute configurations of the novel metabolites.

Main Methods:

• Isolation of metabolites using chromatographic techniques.
• Structure elucidation employing comprehensive 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry (MS).
• Determination of absolute configurations using Electronic Circular Dichroism (ECD) spectroscopy and computational modeling.

Main Results:

• Two new carbasugar-type metabolites, compounds 1 and 2, were successfully isolated and structurally elucidated.
• Compound 1, (1 S,2 R,3 R,4 R,5 R)-2,3,4-trihydroxy-5-methylcyclohexyl-2',5'-dihydroxybenzoate, showed antileishmanial activity with an IC50 of 100 μM.
• Compound 2, (1 S,2 S,3 S,4 R,5 R)-4-[(2',5'-dihydroxybenzyl)oxy]-5-methylcyclohexane-1,2,3-triol, demonstrated potent antileishmanial activity with an IC50 of 57 μM.
• The absolute configurations of both compounds were rigorously assigned using a combination of NMR, ECD, and computational methods.

Conclusions:

• Geosmithia langdonii is a promising source of novel bioactive carbasugar metabolites.
• Compounds 1 and 2 represent new chemical entities with significant antileishmanial potential.
• The structural and stereochemical characterization provides a foundation for further investigation and development of these compounds as anti-leishmanial agents.