ABSTRACT

DNA gyrase B subunit, a druggable target of potent anti-tubercular agents is involved in the process of ATP hydrolysis which in turn provides energy to gyrase A subunit for maintaining the DNA topological state. In the present study, we employed structural optimization of the reported Gyrase B inhibitors possessing quinoline nucleus employing Quantitative Structure-Activity Relationship (QSAR) and docking studies. QSAR studies were carried out by QSARINS software on 4- aminoquinoline derivatives for the best model having four variables L1i, MoRSEN26, RDFM5 and RDFE25 with statistical values R2 = 0.7430, LOF=0.0608, CCCtr = 0.8525, Q2LOO = 0.6461, Q2LMO = 0.6189, CCCcv = 0.7972, R2ext = 0.8294, and CCCext = 0.8898. The developed QSAR model suggests that the 3D-Weighted Holistic Invariant Molecular descriptors (3D-WHIM), 3D- Molecular representations of structure based on electron diffraction descriptors (3D-MoRSE) and Radial Distribution Function (RDF) descriptors play key roles in predicting bioactivity. The designed compounds using QSAR model predicted molecular descriptor information yielded compounds 42a and 42c as good potential theoretical candidates. Binding energy scores of the designed compounds provided nanomolar activity binding interactions in the active site of 3zkd: DNA Gyrase B enzyme. Compound 42a, with predicted activity of ~80nM MIC will be take over for further experimental studies as anti-tubercular lead. Keywords: Anti-mycobacterial activity, Autodock, MoRSE, QSAR
Publication date: 01/04/2023

https://ijbpas.com/pdf/2023/April/MS_IJBPAS_2023_6883.pdf

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https://doi.org/10.31032/IJBPAS/2023/12.4.6883