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α-蒎烯:对接研究、细胞毒性、作用机制及对……的抗生物膜效应

α-Pinene: Docking Study, Cytotoxicity, Mechanism of Action, and Anti-Biofilm Effect against .

作者信息

Bomfim de Barros Daniela, de Oliveira E Lima Luanna, Alves da Silva Larissa, Cavalcante Fonseca Mariana, Ferreira Rafael Carlos, Diniz Neto Hermes, da Nóbrega Alves Danielle, da Silva Rocha Walicyranison Plinio, Scotti Luciana, de Oliveira Lima Edeltrudes, Vieira Sobral Marianna, Cançado Castellano Lúcio Roberto, Moura-Mendes Juliana, Queiroga Sarmento Guerra Felipe, da Silva Márcia Vanusa

机构信息

Department of Biochemistry, Federal University of Pernambuco, Recife 50670-901, PE, Brazil.

Department of Pharmaceutical Sciences, Paraíba Federal University, João Pessoa 58051-900, PB, Brazil.

出版信息

Antibiotics (Basel). 2023 Feb 28;12(3):480. doi: 10.3390/antibiotics12030480.

Abstract

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 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 and toxicity against human cells (HaCaT). Results from the molecular-docking simulation demonstrated that thymidylate synthase (-52 kcal mol), and δ-14-sterol reductase (-44 kcal mol) 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

摘要

与免疫功能低下患者的严重感染有关。萜类是天然产物衍生物,作为抗真菌替代品被广泛研究。在我们小组之前报道的一项研究中,验证了α-蒎烯对[具体真菌未提及]的抗真菌活性;α-蒎烯的最低抑菌浓度在128 - 512 µg/mL之间。在本研究中,我们评估了杀菌动力学、利用计算机模拟和体外试验的作用机制、对[具体真菌未提及]的抗生物膜活性以及对人细胞(HaCaT)的毒性。分子对接模拟结果表明,胸苷酸合成酶(-52千卡/摩尔)和δ-14-甾醇还原酶(-44千卡/摩尔)表现出最佳相互作用。我们的体外结果表明,α-蒎烯的抗真菌活性涉及与细胞膜中的麦角固醇结合。在杀菌动力学试验中,抗真菌活性不具有时间依赖性,还能抑制生物膜形成,同时破坏高达88%的现有生物膜。它对人角质形成细胞无细胞毒性。我们的研究支持α-蒎烯作为治疗由[具体真菌未提及]引起的真菌感染的候选药物

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f89b/10044001/52fee4ddb14a/antibiotics-12-00480-g001a.jpg

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