Department of Chemistry, Savitribai Phule Pune University, Pune, India
Bioinformatics Centre, The Department of Biotechnology and Department of Chemistry, Savitribai Phule Pune University, Pune, India
Comb Chem High Throughput Screen. 2020;23(8):723-739. doi: 10.2174/1386207323666200422082754.
The study aims at the derivatization of "Phthalides" and synthesizes 3- arylaminophthalides & 3-indolyl-phthalides compounds, and evaluates their anti-tubercular and antioxidant activities. The study has also intended to employ the in silico methods for the identification of possible drug targets in Mycobacterium and evaluate the binding affinities of synthesized compounds.
This report briefly explains the synthesis of phthalide derivatives using ammonium chloride. The synthesized compounds were characterized using spectral analysis. Resazurin Microtiter Assay (REMA) plate method was used to demonstrate the anti-mycobacterial activity of the synthesized compounds. An in-silico pharmacophore probing approach was used for target identification in Mycobacterium. The structural level interaction between the identified putative drug target and synthesized phthalides was studied using Lamarckian genetic algorithm-based software.
In the present study, we report an effective, environmentally benign scheme for the synthesis of phthalide derivatives. Compounds 5c and 5d from the current series appear to possess good anti-mycobacterial activity. dCTP: deaminasedUTPase was identified as a putative drug target in Mycobacterium. The docking results clearly showed the interactive involvement of conserved residues of dCTP with the synthesized phthalide compounds.
On the eve of evolving anti-TB drug resistance, the data on anti-tubercular and allied activities of the compounds in the present study demonstrates the enormous significance of these newly synthesized derivatives as possible candidate leads in the development of novel anti-tubercular agents. The docking results from the current report provide a structural rationale for the promising anti-tubercular activity demonstrated by 3-arylaminophthalides and 3-indolyl-phthalides compounds.
本研究旨在对“苯酞”进行衍生化，并合成 3-芳氨基苯酞和 3-吲哚基苯酞化合物，评估它们的抗结核和抗氧化活性。本研究还旨在采用计算机方法鉴定分枝杆菌中的可能药物靶点，并评估合成化合物的结合亲和力。
本报告简要介绍了使用氯化铵合成苯酞衍生物的方法。使用光谱分析对合成的化合物进行了表征。使用 Resazurin 微量滴定板（REMA）法来证明合成化合物的抗分枝杆菌活性。采用基于 Lamarckian 遗传算法的软件进行计算机药理学探测方法，以鉴定分枝杆菌中的潜在药物靶点。研究了鉴定出的假定药物靶标与合成苯酞之间的结构水平相互作用。
在本研究中，我们报告了一种有效、环境友好的苯酞衍生物合成方案。当前系列中的化合物 5c 和 5d 似乎具有良好的抗分枝杆菌活性。dCTP：脱氨酶 dUTPase 被鉴定为分枝杆菌中的潜在药物靶点。对接结果清楚地表明，dCTP 与合成的苯酞化合物的保守残基之间存在相互作用。
在抗结核药物耐药性不断发展的情况下，本研究中化合物的抗结核和相关活性数据表明，这些新合成的衍生物作为新型抗结核药物开发的潜在候选物具有重要意义。本报告的对接结果为 3-芳氨基苯酞和 3-吲哚基苯酞化合物所表现出的有希望的抗结核活性提供了结构依据。
