Infectious diseases such as tuberculosis and leishmaniasis are leading causes of human death. One of the major factors contributing to the poor control of these diseases is primarily the reduced effectiveness of the existing chemotherapies as result of the increasing rise of multidrug-resistant strains of their causative agents. This leads to the imperative need to develop new and effective drugs. In search for such agents, a series of hydroquinone-triazole hybrids was investigated. The design, synthesis, and biological activities against the human virulent H37Rv strain of Mycobacterium tuberculosis (Mtb) and Leishmaniasis major (L. major), causative pathogen of human cutaneous leishmaniasis, are herein reported. The hybrids were synthesized following a two-step process Michael addition and Click chemistry. They were found to be noncytotoxic toward human kidney embryonic cells but expressed poor cellular antileishmanial and antimycobacterial activities. Hybrid 14, 2‐{4‐[(phenylsulfanyl)methyl]‐1H‐1,2,3‐triazol‐1‐yl}benzene‐1,4‐diol, was the most active among synthesized molecules, with MIC₉₀ 16 and IC₅₀ 23 µM against Mtb and L. major parasite, respectively, but had a poor safety profile, being as toxic to mammalian cells as to mycobacteria and parasites. Thus, compound 14 did not stand as potential anti-infective hit for further investigation. Future endeavor will focus on the investigation of more rigid and flexible hybrids of both scaffolds in order to assess the impact a spacer might have on their biological activity.

中文翻译：

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对苯二酚-三唑杂化物的合成及其体外抗分枝杆菌和抗真菌活性

结核病和利什曼病等传染病是人类死亡的主要原因。导致这些疾病控制不佳的主要因素之一，主要是由于其病原体的多药耐药株增加，导致现有化学疗法的有效性下降。这导致迫切需要开发新的有效药物。为了寻找这种试剂，研究了一系列氢醌-三唑杂化物。抗人结核分枝杆菌（Mtb）和利什曼原虫病（L. major）的H37Rv毒株的设计，合成和生物学活性。本文报道了人皮肤利什曼病的致病病原体。按照两步法迈克尔加成法和点击化学法合成杂化物。发现它们对人肾胚胎细胞无细胞毒性，但表达的细胞抗衰老和抗分枝杆菌活性较弱。混合动力车14，2- {4 - [（苯基硫基）甲基] -1 ħ -1,2,3-三唑-1-基}苯-1,4-二醇，是合成的分子中最活跃，MIC ₉₀ 16和IC ₅₀ 23 µM分别针对Mtb和L.主要寄生虫，但安全性较差，对哺乳动物细胞的毒性与对分枝杆菌和寄生虫的毒性相同。因此，化合物14没有作为潜在的抗感染药物进行进一步调查。未来的工作将集中在研究两种支架的刚性和柔性更强的杂种上，以评估间隔物对其生物学活性的影响。