Antifungal Polybrominated Proxyphylline Derivative Induces Candida albicans Calcineurin Stress Response in Galleria mellonella.

Antifungal Polybrominated Proxyphylline Derivative Induces Candida albicans Calcineurin Stress Response in Galleria mellonella.
Bioorg Med Chem Lett. 2020 Sep 12;:127545
Authors: Gizińska M, Staniszewska A, Kazek M, Koronkiewicz M, Kuryk Ł, Milner-Krawczyk M, Baran J, Borowiecki P, Staniszewska M
Abstract
Candida albicans CNB1 plays a role in the response in vitro and in vivo to stress generated by PB-WUT-01, namely 1,3-dimethyl-7-(2-((1-(3-(perbromo-2H-benzo[d][1,2,3]triazol-2-yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)propyl)-1H-purine-2,6(3H,7H)-dione. The antifungal mechanism involved the calcineurin pathway-regulated genes SAP9-10. Galleria mellonella treated with PB-WUT-01 (at 0.64 µg/mg) showed limited candidiasis and remained within the highest survival rates. The molecular mode of action of PB-WUT-01 was rationalized by in silico docking studies toward both human and C. albicans calcineurin A (CNA) and calcineurin B (CNB) complexes, respectively. PB-WUT-01 acting as a calcineurin inhibitor in the C. albicans cells enhances the cells' susceptibility. Therefore it could be a suitable alternative treatment in patients with candidiasis.
PMID: 32931913 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - September 11, 2020 Category: Chemistry Authors: Gizińska M, Staniszewska A, Kazek M, Koronkiewicz M, Kuryk Ł, Milner-Krawczyk M, Baran J, Borowiecki P, Staniszewska M Tags: Bioorg Med Chem Lett Source Type: research