α-Pinene: Docking Study, Cytotoxicity, Mechanism of Action, and Anti-Biofilm Effect against <i>Candida albicans</i>
Daniela Bomfim de Barros,
Luanna de Oliveira e Lima,
Larissa Alves da Silva,
Mariana Cavalcante Fonseca,
Rafael Carlos Ferreira,
Hermes Diniz Neto,
Danielle da Nóbrega Alves,
Walicyranison Plinio da Silva Rocha,
Luciana Scotti,
Edeltrudes de Oliveira Lima,
Marianna Vieira Sobral,
Lúcio Roberto Cançado Castellano,
Juliana Moura-Mendes,
Felipe Queiroga Sarmento Guerra,
Márcia Vanusa da Silva
Affiliations
Daniela Bomfim de Barros
Department of Biochemistry, Federal University of Pernambuco, Recife 50670-901, PE, Brazil
Luanna de Oliveira e Lima
Department of Pharmaceutical Sciences, Paraíba Federal University, João Pessoa 58051-900, PB, Brazil
Larissa Alves da Silva
Department of Pharmaceutical Sciences, Paraíba Federal University, João Pessoa 58051-900, PB, Brazil
Mariana Cavalcante Fonseca
Department of Pharmaceutical Sciences, Paraíba Federal University, João Pessoa 58051-900, PB, Brazil
Rafael Carlos Ferreira
Postgraduate Program in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil
Hermes Diniz Neto
University Hospital Julio Muller, Federal University of Mato Grosso, Cuiabá 78060-900, MT, Brazil
Danielle da Nóbrega Alves
Department of Clinical and Social Dentistry, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil
Walicyranison Plinio da Silva Rocha
Department of Pharmaceutical Sciences, Paraíba Federal University, João Pessoa 58051-900, PB, Brazil
Luciana Scotti
Cheminformatics Laboratory, Postgraduate Program in Natural Products and Synthetic Bioactive, Quality Management, University Hospital, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil
Edeltrudes de Oliveira Lima
Department of Pharmaceutical Sciences, Paraíba Federal University, João Pessoa 58051-900, PB, Brazil
Marianna Vieira Sobral
Postgraduate Program in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil
Lúcio Roberto Cançado Castellano
Human Immunology Research and Education Group-GEPIH, Technical School of Health, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil
Juliana Moura-Mendes
Centro Multidisciplinario de Investigaciones Tecnológicas, Universidad Nacional de Asunción, San Lorenzo 111421, Paraguay
Felipe Queiroga Sarmento Guerra
Department of Pharmaceutical Sciences, Paraíba Federal University, João Pessoa 58051-900, PB, Brazil
Márcia Vanusa da Silva
Department of Biochemistry, Federal University of Pernambuco, Recife 50670-901, PE, Brazil
Candida albicans is associated with serious infections in immunocompromised patients. Terpenes are natural-product derivatives, widely studied as antifungal alternatives. In a previous study reported by our group, the antifungal activity of α-pinene against C. albicans was verified; α-pinene presented an MIC between 128–512 µg/mL. In this study, we evaluate time-kill, a mechanism of action using in silico and in vitro tests, anti-biofilm activity against the Candida albicans, and toxicity against human cells (HaCaT). Results from the molecular-docking simulation demonstrated that thymidylate synthase (−52 kcal mol−1), and δ-14-sterol reductase (−44 kcal mol−1) presented the best interactions. Our in vitro results suggest that α-pinene’s antifungal activity involves binding to ergosterol in the cellular membrane. In the time-kill assay, the antifungal activity was not time-dependent, and also inhibited biofilm formation, while rupturing up to 88% of existing biofilm. It was non-cytotoxic to human keratinocytes. Our study supports α-pinene as a candidate to treat fungal infections caused by C. albicans.
