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Diphenyl diselenide and its interaction with antifungals against Aspergillus spp.
Medical Mycology ( IF 2.9 ) Pub Date : 2020-08-25 , DOI: 10.1093/mmy/myaa072 Aryse Martins Melo 1, 2, 3 , Vanice Rodrigues Poester 3, 4 , Mariana Trapaga 3 , Cristina Wayne Nogueira 5 , Gilson Zeni 5 , Marife Martinez 6 , Gabriele Sass 6 , David A Stevens 6, 7 , Melissa Orzechowski Xavier 1, 3, 4, 6
Medical Mycology ( IF 2.9 ) Pub Date : 2020-08-25 , DOI: 10.1093/mmy/myaa072 Aryse Martins Melo 1, 2, 3 , Vanice Rodrigues Poester 3, 4 , Mariana Trapaga 3 , Cristina Wayne Nogueira 5 , Gilson Zeni 5 , Marife Martinez 6 , Gabriele Sass 6 , David A Stevens 6, 7 , Melissa Orzechowski Xavier 1, 3, 4, 6
Affiliation
Given the few antifungal classes available to treat aspergillosis, this study aimed to evaluate the in vitro antifungal activity of diphenyl diselenide (PhSe)2 alone and in combination with classical antifungals against Aspergillus spp., and its in vivo activity in a systemic experimental aspergillosis model. We performed in vitro broth microdilution assay of (PhSe)2 against 32 Aspergillus isolates; and a checkboard assay to test the interaction of this compound with itraconazole (ITC), voriconazole (VRC), amphotericin B (AMB), and caspofungin (CAS), against nine Aspergillus isolates. An experimental model of invasive aspergillosis in mice was studied, and survival curves were compared between an untreated group and groups treated with 100 mg/kg ITC, or (PhSe)2 in different dosages (10 mg/kg, 50 mg/kg and 100 mg/kg). All Aspergillus non-fumigatus and 50% of A. fumigatus were inhibited by (PhSe)2 in concentrations ≤ 64 µg/ml, with significant differences in MICs between the sections. Synergism or additive effect in the in vitro (PhSe)2 interaction with VRC and CAS was observed against the majority of isolates, and with ITC against the non-fumigatus strains. In addition to the inhibitory interaction, (PhSe)2 was able to add a fungicidal effect to CAS. Survival curves from the systemic experimental aspergillosis model demonstrated that the inoculum caused an acute and lethal infection in mice, and no treatment applied significantly prolonged survival over that of the control group. The results highlight the promising activity of (PhSe)2 against Aspergillus species, but more in vivo studies are needed to determine its potential applicability in aspergillosis treatment.
中文翻译：
二苯基二硒化物及其与抗曲霉属的抗真菌剂的相互作用。
鉴于可用于治疗曲霉病的抗真菌药物种类很少，本研究旨在评估二苯基二硒化物 (PhSe) 2单独和与经典抗真菌药物联合使用对曲霉属的体外抗真菌活性，以及其在系统性实验曲霉病模型中的体内活性. 我们对 32种曲霉分离株进行了 (PhSe) 2 的体外肉汤微量稀释测定；以及一个棋盘式试验，以测试该化合物与伊曲康唑 (ITC)、伏立康唑 (VRC)、两性霉素 B (AMB) 和卡泊芬净 (CAS) 对九种曲霉的相互作用隔离。研究了小鼠侵袭性曲霉病的实验模型，比较了未治疗组与不同剂量（10 mg/kg、50 mg/kg 和 100 mg/kg ITC 或 (PhSe) 2治疗组）的生存曲线。毫克/公斤）。所有非烟曲霉和50% 的烟曲霉都被 (PhSe) 2抑制，浓度 ≤ 64 µg /ml，各切片之间的 MIC 有显着差异。在体外(PhSe) 2 与 VRC 和 CAS 的相互作用中观察到对大多数分离株的协同作用或相加效应，以及与 ITC 对非烟曲霉属的相互作用菌株。除了抑制相互作用外，(PhSe) 2还能够为 CAS 添加杀菌作用。来自全身性实验曲霉病模型的存活曲线表明，接种物在小鼠中引起急性和致命感染，并且与对照组相比，没有应用显着延长存活时间的治疗。结果突出了 (PhSe) 2对曲霉属物种的有希望的活性，但需要更多的体内研究来确定其在曲霉病治疗中的潜在适用性。
更新日期：2020-08-26
中文翻译：
二苯基二硒化物及其与抗曲霉属的抗真菌剂的相互作用。
鉴于可用于治疗曲霉病的抗真菌药物种类很少，本研究旨在评估二苯基二硒化物 (PhSe) 2单独和与经典抗真菌药物联合使用对曲霉属的体外抗真菌活性，以及其在系统性实验曲霉病模型中的体内活性. 我们对 32种曲霉分离株进行了 (PhSe) 2 的体外肉汤微量稀释测定；以及一个棋盘式试验，以测试该化合物与伊曲康唑 (ITC)、伏立康唑 (VRC)、两性霉素 B (AMB) 和卡泊芬净 (CAS) 对九种曲霉的相互作用隔离。研究了小鼠侵袭性曲霉病的实验模型，比较了未治疗组与不同剂量（10 mg/kg、50 mg/kg 和 100 mg/kg ITC 或 (PhSe) 2治疗组）的生存曲线。毫克/公斤）。所有非烟曲霉和50% 的烟曲霉都被 (PhSe) 2抑制，浓度 ≤ 64 µg /ml，各切片之间的 MIC 有显着差异。在体外(PhSe) 2 与 VRC 和 CAS 的相互作用中观察到对大多数分离株的协同作用或相加效应，以及与 ITC 对非烟曲霉属的相互作用菌株。除了抑制相互作用外，(PhSe) 2还能够为 CAS 添加杀菌作用。来自全身性实验曲霉病模型的存活曲线表明，接种物在小鼠中引起急性和致命感染，并且与对照组相比，没有应用显着延长存活时间的治疗。结果突出了 (PhSe) 2对曲霉属物种的有希望的活性，但需要更多的体内研究来确定其在曲霉病治疗中的潜在适用性。
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