In this study, a series of novel thiazol-2(3H)-imine (2a–2j) were designed, synthesized, and characterized by means of ¹H NMR, ¹³C NMR, and HRMS spectral analyses. In vitro antifungal activity was performed using a modified EUCAST protocol. Two of the synthesized compounds (2d and 2e) showed activity against Candida albicans and Candida parapsilosis. Compound 2e showed activity against C. parapsilosis (MIC₅₀ = 1.23 μg/mL) for 48 h. This value is very similar to ketoconazole. The dynamic analysis of the potential compounds 2d and 2e revealed notable stability while interacting with the 14α-demethylase enzyme substrate. The absorption, distribution, metabolism, and excretion (ADME) studies of the candidate compound showed acceptable ADME parameter data and verified their drug-likeness characteristics. According to the results of this study, compound 4-(4-fluorophenyl)-N-(3-morpholinopropyl)-3-phenylthiazol-2(3H)-imine (2e) and its derivatives as 14α-demethylase inhibitors can be used as a new antifungal for further structural improvements and additional research.

中文翻译：

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(4-取代苯基)-N-(3-吗啉代丙基)-3-苯基噻唑-2(3H)-亚胺衍生物作为抗真菌剂的设计、合成、研究和生物活性评估


在本研究中，设计、合成了一系列新型噻唑-2(3 H )-亚胺( 2a – 2j )，并通过¹ H NMR、 ¹³ C NMR 和 HRMS 光谱分析对其进行了表征。使用修改后的 EUCAST 方案进行体外抗真菌活性。两种合成的化合物（ 2d和2e ）显示出对抗白色念珠菌和近平滑念珠菌的活性。化合物2e显示出对抗C. parapsilosis 的活性 (MIC ₅₀ = 1.23 μg/mL)，持续 48 小时。该值与酮康唑非常相似。潜在化合物2d和2e的动态分析表明，在与 14α-去甲基酶底物相互作用时具有显着的稳定性。候选化合物的吸收、分布、代谢和排泄（ADME）研究显示了可接受的 ADME 参数数据并验证了其药物相似特性。根据本研究结果，化合物4-(4-氟苯基) -N- (3-吗啉代丙基)-3-苯基噻唑-2( 3H )-亚胺( 2e )及其衍生物可作为14α-去甲基酶抑制剂作为一种新的抗真菌药物，用于进一步的结构改进和额外的研究。