Inhibition of the morphological transition of Candida spp. by riparins I-IV.

Autor: Queiroz da Silva ML; Departamento de Química Biológica, Universidade Regional do Cariri (URCA), Crato, Brazil., Ferreira de Sousa N; Laboratório de Quimioinformática, Departamento de Química, Universidade Federal da Paraíba (UFPB), São João do Cariri, Brazil., Dos Santos ATL; Departamento de Química Biológica, Universidade Regional do Cariri (URCA), Crato, Brazil., de Sousa GR; Departamento de Ciências da Saúde, Universidade Federal da Paraiba (UFPB), São João do Cariri, Brazil., Fonseca VJA; Departamento de Química Biológica, Universidade Regional do Cariri (URCA), Crato, Brazil., Douglas Melo Coutinho H; Departamento de Química Biológica, Universidade Regional do Cariri (URCA), Crato, Brazil., Barbosa Filho JM; Departamento de Ciências da Saúde, Universidade Federal da Paraiba (UFPB), São João do Cariri, Brazil., de Souza Ferrari J; Departamento de Química, Universidade Federal da Paraíba (UFPB), São João do Cariri, Brazil., Scotti MT; Laboratório de Quimioinformática, Departamento de Química, Universidade Federal da Paraíba (UFPB), São João do Cariri, Brazil., Ribeiro-Filho J; Oswaldo Cruz Foundation (Fiocruz), Fiocruz Ceará, Eusébio, Brazil., Martins de Lima JP; CECAPE College, Juazeiro do Norte, Brazil., da Rocha JBT; Departamento de Química Biológica, Universidade Regional do Cariri (URCA), Crato, Brazil.; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil., Bezerra Morais-Braga MF; Departamento de Ciências Biológica, Universidade Regional do Cariri (URCA), Crato, Brazil.
Jazyk: angličtina
Zdroj: Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2024 Oct; Vol. 38 (5), pp. 946-957. Date of Electronic Publication: 2024 May 13.
DOI: 10.1111/fcp.13007
Abstrakt: Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide-type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N-acetylglucosamine, CYP-51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP-51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus.
(© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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