Abstract：
Inspired from the important applications of spirocyclic compounds in medicinal chemistry, a new series of pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids was reported via Cu(I)-catalyzed click reaction from isatin-pyrazoline linked terminal alkynes with in situ derived benzyl azides. Antimicrobial evaluation data showed that all hybrids exhibited promising efficacy towards the tested microbial strains. Antimicrobial screening as well as docking studies suggested that hybrid 6a was found to be most potent towards Aspergillus niger (MIC = 0.0122 μmol/mL) and Escherichia coli (MIC = 0.0061 μmol/mL). Molecular docking studies of 6a within the binding pockets of antibacterial and antifungal targets revealed good interactions with the binding energies of - 144.544 kcal/mol and - 154.364 kcal/mol against 1KZN (E. coli) and 3D3Z (A. niger), respectively. Further, MD simulations were performed to study the stability of the complexes formed at 300 K. Based on the RMSD trajectories, it is evident that 3D3Z-6a complex exhibits minimal deviation, whereas the 1KZN-6a complex displayed little more deviation compared to the protein but, both are in acceptable range. Moreover, 3D3Z-6a and 1KZN-6a showed maximum number of hydrogen bonds at 50 ns and 70 ns, respectively, thereby complementing the stability of these complexes.
摘要：
灵感来自螺环化合物在药物化学中的重要应用，报道了一系列新的吡唑啉螺-羟吲哚系链的1,2,3-三唑杂化物，通过Cu（I）催化的点击反应，该点击反应来自与原位衍生的苄基叠氮化物连接的Iatin-吡唑啉末端炔烃。抗微生物评估数据表明，所有杂种对测试的微生物菌株均表现出有希望的功效。抗菌筛选和对接研究表明，发现杂种6a对黑曲霉（MIC=0.0122μmol/mL）和大肠杆菌（MIC=0.0061μmol/mL）最有效。在抗菌和抗真菌靶标的结合袋中对6a的分子对接研究表明，与-144.544kcal/mol和-154.364kcal/mol的结合能对1KZN（E.大肠杆菌)和3D3Z(A.尼日尔)，分别。Further,进行MD模拟以研究在300K形成的复合物的稳定性。基于RMSD轨迹，很明显，3D3Z-6a复合物表现出最小的偏差，而与蛋白质相比，1KZN-6a复合物显示出更多的偏差，但两者都在可接受的范围内。此外，3D3Z-6a和1KZN-6a在50ns和70ns时显示出最大的氢键数，分别,从而补充这些复合物的稳定性。
