Naphthoquinones biflorin and bis-biflorin (Capraria biflora) as possible inhibitors of the fungus Candida auris polymerase: molecular docking, molecular dynamics, MM/GBSA calculations and in silico drug-likeness study

Abstract

A new worldwide concern has emerged with the recent emergence of infections caused by Candida auris. This reflects its comparative ease of transmission, substantial mortality, and the increasing level of resistance seen in the three major classes of antifungal drugs. Efforts to create a better design for structure-based drugs that described numerous modifications and the search for secondary metabolic structures derived from plant species are likely to reduce the virulence of several fungal pathogens. In this context, the present work aimed to evaluate in silico two naphthoquinones isolated from the roots of Capraria biflora, biflorin, and its dimmer, bis-biflorin, as potential inhibitors of Candida auris polymerase. Based on the simulation performed with the two naphthoquinones, biflorin and bis-biflorin, it can be stated that bis-biflorin showed the best interactions with Candida auris polymerase. Still, biflorin also demonstrated favorable coupling energy. Predictive pharmacokinetic assays suggest that biflorin has high oral bioavailability and more excellent metabolic stability compared to the bis-biflorin analogue. constituting a promising pharmacological tool.

Communicated by Ramaswamy H. Sarma

Keywords:

• receptor
• ligand
• molecular docking
• superfungus
• pharmacokinetics and metabolism

Acknowledgments

The authors would like to thank the Brazilian Agencies: Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Ensino Superior (CAPES) for fellowships and financial supports.

Disclosure statement

Authors also declare no conflict of interest.

Funding

Hélcio S. Santos acknowledges financial support from the PQ/BPI-FUNCAP (Grant BP4-0172-00075.01.00/20).