α-Pinene: Docking Study, Cytotoxicity, Mechanism of Action, and Anti-Biofilm Effect against Candida albicans .
Daniela Bomfim de BarrosLuanna de Oliveira E LimaLarissa Alves da SilvaMariana Cavalcante FonsecaRafael Carlos FerreiraHermes Diniz-NetoDanielle da Nóbrega AlvesWalicyranison Plinio da Silva RochaLuciana ScottiEdeltrudes de Oliveira LimaMarianna Vieira SobralLúcio Roberto Cançado CastellanoJuliana Moura MendesFelipe Queiroga Sarmento GuerraMárcia Vanusa da SilvaPublished in: Antibiotics (Basel, Switzerland) (2023)
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.