Abstract

A heterogeneous, inexpensive and eco-friendly graphene oxide (GO) catalyst empowered the formation of bioactive biscoumarin derivatives involving domino Knoevenagel–Michael condensation using 4-hydroxycoumarin and aromatic aldehydes in H₂O: EtOH solvent system. The prepared GO was well characterized by Fourier transform infrared (FT-IR), X-ray diffraction spectroscopy (XRD), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and thermogravimetric analysis (TGA). In this efficient, green, and sustainable one-pot synthesis, the target products were obtained in excellent yields (76–97%) in short reaction time (10–20 min.) and the catalyst can be easily recoverable and reusable for five consecutive cycles. Moreover, the use of economical and easily available substrate, low catalyst loading, shorter reaction time, gram scale applicability and high atom economy are the additional advantages of this greener approach. The inhibitory activity of the synthesized compounds was tested against two species of Gram-negative bacteria (E.Coli MTCC 46 and P. aeruginosa MTCC 2488), two species of Gram-positive bacteria (S. aureus MTCC 6980 and B. megaterium MTCC) and fungus (A. niger MTCC 1344) using the broth microdilution method. The electron withdrawing substituents like -CN, –F, and –Cl exhibited excellent activity against gram negative bacteria as compared to gram positive bacteria. Additionally, in silico studies were carried out on the selected DNA gyrase (1KZN) and human lanosterol 14 alpha-demethylase CYP51 (3LD6) to study the docking interactions of the synthesized compounds. It was observed that out of all the docked compounds, 4e (−23.966 kcal/mol) and 4i (−24.976 kcal/mol) showed highest docking score against 1KZN and 3LD6 protein, respectively.

摘要

一种非均相、廉价且环保的氧化石墨烯 (GO) 催化剂能够在 H _{2中使用 4-羟基香豆素和芳香醛形成生物活性双香豆素衍生物，包括多米诺 Knoevenagel-Michael 缩合}O：乙醇溶剂系统。制备的GO通过傅里叶变换红外（FT-IR）、X射线衍射光谱（XRD）、场发射扫描电子显微镜（FE-SEM）、原子力显微镜（AFM）和热重分析（TGA）进行了很好的表征。在这种高效、绿色和可持续的一锅法合成中，目标产物在很短的反应时间（10-20 分钟）内以优异的收率（76-97%）获得，并且催化剂可以很容易地回收和重复使用五次循环。此外，使用经济且易于获得的底物、低催化剂负载、更短的反应时间、克级适用性和高原子经济性是这种更环保方法的额外优势。合成的化合物对两种革兰氏阴性菌的抑制活性进行了测试（大肠杆菌MTCC 46 和铜绿假单胞菌MTCC 2488）、两种革兰氏阳性细菌（金黄色葡萄球菌MTCC 6980 和巨大芽孢杆菌MTCC）和真菌（黑曲霉MTCC 1344）使用肉汤微量稀释法。与革兰氏阳性菌相比，-CN、-F 和-Cl 等吸电子取代基对革兰氏阴性菌表现出优异的活性。此外，对选定的 DNA 促旋酶 (1KZN) 和人羊毛甾醇 14 α-去甲基化酶 CYP51 (3LD6) 进行了计算机研究，以研究合成化合物的对接相互作用。据观察，在所有对接的化合物中，4e (-23.966 kcal/mol) 和4i(-24.976 kcal/mol) 分别显示对 1KZN 和 3LD6 蛋白的最高对接分数。