Anti-Sporotrichotic Activity, Lambert-W Inhibition Kinetics and 3D Structural Characterization of Sporothrix schenckii Catalase as Target of Glucosinolates from Moringa oleifera

IF 2.3 Q3 PHARMACOLOGY & PHARMACY Scientia Pharmaceutica Pub Date : 2022-11-04 DOI:10.3390/scipharm90040070
E. Sierra-Campos, M. Valdez-Solana, E. Ruiz-Baca, Erica K. Ventura-García, Claudia Avitia-Domínguez, M. Aguilera-Ortíz, A. Téllez-Valencia
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Abstract

Most human fungal infections exhibit significant defensive oxidative stress responses, which contribute to their pathogenicity. An important component of these reactions is the activation of catalase for detoxification. To discover new antifungal chemicals, the antifungal activity of methanol extracts of Moringa oleifera from two commercial products (Akuanandi and Mas Lait) was investigated. The methanolic extracts’ activity against Sporothrix schenckii was determined using an assay for minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC). The MIC concentrations varied between 0.5 μg/mL and 8 μg/mL. Akuanandi extract had the lowest MIC (0.5 μg/mL) and MLC (1 μg/mL) values. M. oleifera methanolic extracts were tested for catalase inhibition. The Ki values of the M. oleifera extract against S. schenckii catalase (SsCAT) was found to be 0.7 μg/mL for MOE-AK and 0.08 μg/mL for MOE-ML. Catalase’s 3D structure in SsCAT is unknown. The homology of SsCAT was modeled with an in silico study using a 3D structure from SWISS MODEL and validation the predicted 3D structure was carried out using PROCHECK and MolProbity. Docking simulations were used to analyze protein interactions using Pymol, PoseView, and PLIP. The results revealed that M. oleifera glucosinolates interacts with SsCAT. A molecular interaction analysis revealed two inhibitor compounds (glucosinalbin and glucomoringin) with high binding affinity to key allosteric-site residues. The binding energies revealed that glucosinalbin and glucomoringin bind with high affinity to SsCAT (docking energy values: −9.8 and −9.0 kcal/mol, respectively). The findings of this study suggest that glucosinolates derived from M. oleifera could be used instead of synthetic fungicides to control S. schenckii infections. We hope that the findings of this work will be valuable for developing and testing novel natural anti-sporothrix therapeutic agents in the future.
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辣木葡糖酸盐靶向申克氏孢子丝过氧化氢酶的抗孢子丝菌活性、Lambert-W抑制动力学及三维结构表征
大多数人类真菌感染表现出显著的防御性氧化应激反应,这有助于其致病性。这些反应的一个重要组成部分是活化过氧化氢酶解毒。为了发现新的抗真菌化学物质,对两种商品辣木(Akuanandi和Mas Lait)甲醇提取物的抗真菌活性进行了研究。采用最小抑制浓度(MIC)和最小致死浓度(MLC)测定甲醇提取物对申克孢子菌的活性。MIC浓度在0.5 ~ 8 μg/mL之间变化。黄芪提取物的MIC (0.5 μg/mL)和MLC (1 μg/mL)最低。研究了油桐甲醇提取物对过氧化氢酶的抑制作用。结果表明,油菜花提取物对申氏葡萄球菌过氧化氢酶(SsCAT)的Ki值分别为0.7 μg/mL和0.08 μg/mL。过氧化氢酶在SsCAT中的三维结构尚不清楚。利用SWISS MODEL的三维结构对SsCAT的同源性进行了计算机模拟研究,并利用PROCHECK和MolProbity对预测的三维结构进行了验证。对接模拟使用Pymol、PoseView和PLIP分析蛋白质相互作用。结果表明,油橄榄硫代葡萄糖苷与SsCAT相互作用。分子相互作用分析显示,两种抑制剂(glucosinalbin和gluccomoringin)与关键变构位点残基具有高结合亲和力。结合能表明,硫代葡萄糖苷和糖化蛋白与SsCAT的结合具有较高的亲和力(对接能分别为- 9.8和- 9.0 kcal/mol)。本研究结果提示,从油橄榄中提取的硫代葡萄糖苷可代替合成杀菌剂用于控制申克氏葡萄球菌感染。我们希望这项工作的发现将对未来开发和测试新的天然抗孢子菌治疗药物有价值。
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来源期刊
Scientia Pharmaceutica
Scientia Pharmaceutica Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.60
自引率
4.00%
发文量
67
审稿时长
10 weeks
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