Synthesis, comparative in vitro antibacterial, antioxidant and UV fluorescence studies of bis indole Schiff bases and molecular docking with ct-DNA and SARS-CoV-2 Mpro,Luminescence

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Synthesis, comparative in vitro antibacterial, antioxidant and UV fluorescence studies of bis indole Schiff bases and molecular docking with ct-DNA and SARS-CoV-2 Mpro
Luminescence ( IF 3.2 ) Pub Date : 2021-06-04 , DOI: 10.1002/bio.4098
Sugandha Singhal ₁ , Pankaj Khanna ₂ , Leena Khanna ₁

Affiliation

In this study, synthesis of 15 novel bis indole-based Schiff bases (SBs) 4a–4o was conducted by condensation of 2-(1-aminobenzyl)benzimidazole with symmetrical bis-isatins linked via five alkyl chains (n = 2–6). These were subjected to ADME (absorption, distribution, metabolism and excretion), physiochemical properties, molecular docking, in vitro antibacterial and antioxidant studies. The in silico studies indicated lower toxicity with metabolic stability for nearly all the derivatives proving reliability as drug candidates. The comparative antibacterial study against Staphylococcus aureus and Escherichia coli, also showed a superior inhibition than reference drug and their mono counterparts. The increase in linker alkyl chain length and variation of substituents in indole, further predicted increased inhibition, with maximum value for compound 4o at 50 μg/ml. The in vitro calf thymus DNA (ct-DNA) binding ability of compounds 4c, 4f, 4i, 4l, 4 m, 4n, and 4o was evaluated via ultraviolet-visible and fluorescence spectroscopy techniques. A hyperchromic effect was observed with no apparent wavelength shift which predicted for the groove binding mode. A moderate binding constant for 4o, in fluorescence results, confirms groove binding. The molecular docking of 4o with ct-DNA (PDBID:1BNA) and SARS-CoV-2 M^pro (3CL protease, PDBID:6LU7) prove its efficacy as potential DNA binder and antiviral agent.

中文翻译：

双吲哚希夫碱的合成、体外抗菌、抗氧化和紫外荧光对比研究以及与 ct-DNA 和 SARS-CoV-2 Mpro 的分子对接

在这项研究中，15 种新型双吲哚基席夫碱 (SBs) 4a – 4o 的合成是通过 2-(1-氨基苄基)苯并咪唑与对称双靛红通过五个烷基链 ( n = 2-6) 连接而成的. 这些经过 ADME（吸收、分布、代谢和排泄）、理化特性、分子对接、体外抗菌和抗氧化研究。计算机模拟研究表明，几乎所有证明作为候选药物的衍生物具有较低的毒性和代谢稳定性。金黄色葡萄球菌和大肠杆菌的比较抗菌研究，也显示出比参考药物及其单一对应物更好的抑制作用。接头烷基链长度的增加和吲哚中取代基的变化进一步预测了抑制作用的增加，化合物4o 的最大值为50 μg/ml。在体外小牛胸腺DNA（小牛胸腺DNA）的化合物的结合能力4C，4F，4I，4L，4M，4N，和1-40通过紫外-可见和荧光光谱技术进行评价。观察到增色效应，没有明显的波长偏移，这预测了凹槽结合模式。在荧光结果中，4o 的中等结合常数证实了凹槽结合。4o的分子对接ct-DNA (PDBID:1BNA) 和 SARS-CoV-2 M ^pro（3CL 蛋白酶，PDBID:6LU7）证明了其作为潜在 DNA 结合剂和抗病毒剂的功效。

更新日期：2021-06-04

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