Pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids: Design, synthesis, antimicrobial efficacy and molecular modelling studies.

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED
Akanksha Bhukal, Vijay Kumar, Anirudh Pratap Singh Raman, Anil Kumar, Prashant Singh, Kashmiri Lal
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引用次数: 0

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.

Abstract Image

吡唑啉螺-吲哚系链 1,2,3 三唑杂化物:设计、合成、抗菌功效和分子建模研究。
受螺环化合物在药物化学中的重要应用的启发,通过 Cu(I)-catalyzed click reaction,报告了一系列新的吡唑啉-螺-吲哚系 1,2,3- 三唑杂化物,它们是由异汀-吡唑啉连接的末端炔与原位衍生的苄基叠氮化物通过 Cu(I)-catalyzed click reaction 生成的。抗菌评估数据显示,所有杂化物对受试微生物菌株都具有良好的疗效。抗菌筛选和对接研究表明,杂交种 6a 对黑曲霉(MIC = 0.0122 μmol/mL)和大肠杆菌(MIC = 0.0061 μmol/mL)最有效。对 6a 在抗菌和抗真菌靶标结合口袋内的分子对接研究显示,其与 1KZN (大肠杆菌)和 3D3Z (黑僵菌)的结合能分别为 - 144.544 kcal/mol 和 - 154.364 kcal/mol,具有良好的相互作用。根据 RMSD 轨迹,可以明显看出 3D3Z-6a 复合物的偏差极小,而 1KZN-6a 复合物与蛋白质相比偏差稍大,但都在可接受的范围内。此外,3D3Z-6a 和 1KZN-6a 分别在 50 毫微秒和 70 毫微秒时显示出最大氢键数,从而补充了这些复合物的稳定性。
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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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