Searching for antimicrobial and antiviral xanthones: a molecular docking study coupled to multivariate analysis

Xanthones are naturally occurring compounds present almost exclusively in Gentianaceae, Guttiferae, Moraceae, Clusiaceae, and Polygalaceae plant species [1], considering them as chemomarkers. These compounds have demonstrated important biological activities, including DNA-polymerase inhibitory, anti-inflammatory [1] and anti-infective [2,3]. Hence, as part of our current research on virtual screening-aided drug discovery, an in silico study was conducted to evaluate the potential of xanthones as inhibitors of enzymes that play important roles in microorganism metabolic pathways. In depth, molecular docking to more than 200 compounds was carried out employing 10 different receptors of fungal and viral pathogens. Several xanthones exhibited affinity values greater than those for co-crystallized or natural inhibitors. For strongest xanthone – enzyme complexes, detailed analysis of structural interactions and their relevance was accomplished. Molecular docking showed interaction of xanthones with 3 to 10 residues per enzyme. Moreover, affinity values were correlated by means of multivariate statistical analysis. It let to demonstrate partial classification of xanthones and a relationship between affinity and xanthone-type was therefore found. This approach let us to propose at least four hit xanthone structures for anti-infective drugs.

Acknowledgement: The present work is a product derived by the Project IMP-CIAS-1567 financed by Vicerrectoría de Investigaciones at UMNG – Validity 2014.

References:

[1] Negi JS, Bisht VK, Singh P, Rawat MSM, Joshi GP. Naturally Occurring Xanthones: Chemistry and Biology. Journal of Applied Chemistry 2013; ID 621459; doi:10.1155/2013/621459.

[2] Larcher G, et al. Investigation of the antifungal activity of caledonixanthone E and other xanthones against Aspergillus fumigatus. Planta Med 2004; 70: 569 – 571.

[3] Suksamrarn S, et al. Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana. Chem Pharm Bull 2003; 51: 857 – 859.