背景:真菌感染对其治疗管理提出了巨大挑战。由于现有药物分子在大流行感染中的耐药性和毒性,像COVID-19一样,迫切需要找到新的活性分子衍生物,对真菌感染有效。
目的:在本研究中,我们的目标是设计吡唑衍生物使用分子模拟研究针对目标1EA1和合成10分子的吡唑衍生物使用多步合成方法。
方法:设计的吡唑衍生物是通过常规有机方法合成的。利用FT-IR对新合成的吡唑分子进行了表征,1HNMR,13CNMR,和LC-MS技术。还进行了分子对接研究。使用孔板方法在体外评估了新合成化合物对白色念珠菌和黑曲霉的抗真菌活性。
结果:两种化合物,已发现OK-7和OK-8显示与靶蛋白1EA1的显著对接相互作用。还发现,与标准氟康唑相比,这两种化合物对白色念珠菌和黑曲霉显示出显著的抗真菌活性。已发现这两种化合物的最低抑制浓度(MIC)值为50μg/ml。
结论:吡唑衍生物与-CH3,CH3O-,和-CN基团已被发现对测试的真菌具有活性,并且可以进一步探索它们作为在药物化学领域应用的有前途的抗真菌剂的潜力。
BACKGROUND: Fungal infections have posed a big challenge in the management of their treatment. Due to the resistance and toxicity of existing drug molecules in the light of pandemic infections, like COVID-19, there is an urgent need to find newer derivatives of active molecules, which can be effective in fungal infections.
OBJECTIVE: In the present study, we aimed to design
pyrazole derivatives using molecular modeling studies against target 1EA1 and synthesize 10 molecules of
pyrazole derivatives using a multi-step synthesis approach.
METHODS: Designed
pyrazole derivatives were synthesized by conventional organic methods. The newly synthesized
pyrazole molecules were characterized by using FT-IR, 1HNMR, 13CNMR, and LC-MS techniques. Molecular docking studies were also performed. The antifungal activity of newly synthesized compounds was assessed in vitro against Candida albicans and Aspergillus niger using the well plate method.
RESULTS: Two of the compounds, OK-7 and OK-8, have been found to show significant docking interaction with target protein 1EA1. These two compounds have also been found to show significant anti-fungal activity against Candida albicans and Aspergillus nigra when compared to the standard fluconazole. The Minimum Inhibitory Concentration (MIC) value of these two compounds has been found to be 50 μg/ml.
CONCLUSIONS: Pyrazole derivatives with -CH3, CH3O-, and -CN groups have been found to be active against tested fungi and can be further explored for their potential as promising anti-fungal agents for applications in the field of medicinal chemistry.