Departamento de Química Orgánica-Laboratorio de Síntesis de Fármacos Heterocíclicos, Escuela Nacional de Ciencias Biológicas-IPN, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, C.P. 11340 Ciudad de México, Mexico.
Departamento de Microbiología-Laboratorio de Biología Molecular de Bacterias y Levaduras, Escuela Nacional de Ciencias Biológicas-IPN, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, C.P. 11340 Ciudad de México, Mexico.
Molecules. 2018 Mar 7;23(3):599. doi: 10.3390/molecules23030599.
A series of 3-benzoyl imidazo[1,2-]pyrimidines, obtained from -heteroarylformamidines in good yields, was tested in silico and in vitro for binding and inhibition of seven species ( (ATCC 10231), (CD36), (CBS138), (ATCC 6260), , (ATCC 6358) and (MYA-3404)). To predict binding mode and energy, each compound was docked in the active site of the lanosterol 14α-demethylase enzyme (CYP51), essential for fungal growth of species. Antimycotic activity was evaluated as the 50% minimum inhibitory concentration (MIC50) for the test compounds and two reference drugs, ketoconazole and fluconazole. All test compounds had a better binding energy (range: -6.11 to -9.43 kcal/mol) than that found for the reference drugs (range: 48.93 to -6.16 kcal/mol). In general, the test compounds showed greater inhibitory activity of yeast growth than the reference drugs. Compounds and were the most active, indicating an important role in biological activity for the benzene ring with electron-withdrawing substituents. These compounds show the best MIC50 against C. respectively. The current findings suggest that the 3-benzoyl imidazo[1,2-]pyrimidine derivatives, herein synthesized by an accessible methodology, are potential antifungal drugs.
一系列 3-苯甲酰基咪唑并[1,2-a]嘧啶，由 -杂芳基甲脒以较好的产率得到，在体外和计算机模拟中对七种 进行了结合和抑制测试： (ATCC 10231)、 (CD36)、 (CBS138)、 (ATCC 6260)、 (CBS141)、 (CBS1184) 和 (CBS1004)。为了预测结合模式和能量，将每个化合物对接在羊毛甾醇 14α-去甲基酶（CYP51）的活性部位，这对于七种 的真菌生长是必需的。抗真菌活性作为测试化合物和两种参考药物酮康唑和氟康唑的 50%最小抑菌浓度（MIC50）进行评估。所有测试化合物的结合能（范围：-6.11 至-9.43 kcal/mol）都优于参考药物（范围：48.93 至-6.16 kcal/mol）。总的来说，测试化合物对酵母生长的抑制活性大于参考药物。化合物 和 是最活跃的，表明苯环上带有吸电子取代基对生物活性有重要作用。这些化合物对 C. 分别显示出最佳的 MIC50。目前的研究结果表明，通过可访问的方法合成的 3-苯甲酰基咪唑并[1,2-a]嘧啶衍生物可能是潜在的抗真菌药物。
