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Selective photoinactivation of Histoplasma capsulatum by water-soluble derivatives chalcones

机译：水溶性衍生物查耳酮对荚膜胞浆菌的选择性光灭活

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Histoplasmosis is a respiratory and systemic disease caused by the dimorphic fungus Histoplasma capsulatum. The clinical features may vary from asymptomatic infections to disseminated severe form depending of patient immunity. The treatment of histoplasmosis can be performed with itraconazole, fluconazole, and in the disseminated forms is used amphotericin B. However, the critical side effects of amphotericin B, the cases of itraconazole therapy failure and the appearance of fluconozole-resistant strains makes necessary the search of new strategies to treat this disease. Antimicrobial photodynamic therapy (aPDT) seems to be a potential candidate once have been show efficacy to inhibit others dimorphic fungi. Although the photosensitizer (PS) chalcone aggregates in biological medium, it has antifungal activity and show a high quantum yield of ROS formation. So, the aim of this study was to obtain the experimental parameters to achieve an acceptable selective chalcone water-soluble derivatives photoinactivation of H. capsulatum comparing with fibroblastic and keratinocytes cells which are the constituents of some potential host tissues. Yeast and cells were incubated with the same chalchones concentrations and short incubation time followed by irradiation with equal dose of light. The best conditions to kill H. capsulatum selectively were very low photosensitizers concentration (1.95 mu g mL(-1)) incubated by 15 min and irradiated with LED 450 nm with 24 J cm(-2). Key words: chalcone, Histoplasma capsulatum, aPDT, selectivity. (C) 2017 Elsevier B.V. All rights reserved.
机译：组织胞浆菌病是由二形性真菌荚膜胞浆菌引起的呼吸系统疾病。根据患者的免疫力，临床特征可能从无症状感染到弥散性严重形式不等。可以使用伊曲康唑，氟康唑进行组织胞浆菌病的治疗，并以两性霉素B的散布形式进行治疗。但是，两性霉素B的严重副作用，伊曲康唑治疗失败的情况以及对氟康唑耐药的菌株的出现使得进行搜索成为必要治疗该疾病的新策略。一旦已经显示出抑制其他双态真菌的功效，则抗菌光动力疗法（aPDT）似乎是潜在的候选药物。尽管光敏剂（PS）查尔酮在生物介质中聚集，但它具有抗真菌活性，并显示出ROS形成的高量子产率。因此，本研究的目的是获得与某些潜在宿主组织组成成分的成纤维细胞和角质形成细胞相比，获得可接受的荚膜嗜血杆菌选择性查尔酮水溶性衍生物光灭活的实验参数。酵母和细胞以相同的挑战浓度孵育，孵育时间短，然后用等剂量的光照射。选择性杀死kill荚膜的最佳条件是非常低的光敏剂浓度（1.95μg mL（-1））孵育15分钟，并用24 J cm（-2）的LED 450 nm照射。关键词：查尔酮，荚膜组织胞浆，aPDT，选择性。 （C）2017 Elsevier B.V.保留所有权利。

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