A comparative modeling and molecular docking study on Mycobacterium tuberculosis targets involved in peptidoglycan biosynthesis

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

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MoS2–Calix[4]arene Catalyzed Synthesis and Molecular Docking Study of 2,4,5-Trisubstituted Imidazoles As Potent Inhibitors of Mycobacterium tuberculosis

ACS Combinatorial Science ◽

10.1021/acscombsci.0c00038 ◽

2020 ◽

Vol 22 (10) ◽

pp. 509-518

Author(s):

Madihalli S. Raghu ◽

Chikkur B. Pradeep Kumar ◽

Kodalapura N. Nagendra Prasad ◽

Maralekere K. Prashanth ◽

Yogesh K. Kumarswamy ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Molecular Docking ◽

Docking Study ◽

Molecular Docking Study

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Preparation, biological evaluation and molecular docking study of imidazolyl dihydropyrimidines as potential Mycobacterium tuberculosis dihydrofolate reductase inhibitors

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2016.06.082 ◽

2016 ◽

Vol 26 (16) ◽

pp. 4030-4035 ◽

Cited By ~ 14

Author(s):

N.C. Desai ◽

A.R. Trivedi ◽

Vijay M. Khedkar

Keyword(s):

Mycobacterium Tuberculosis ◽

Molecular Docking ◽

Dihydrofolate Reductase ◽

Docking Study ◽

Biological Evaluation ◽

Molecular Docking Study ◽

Reductase Inhibitors ◽

Dihydrofolate Reductase Inhibitors

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In Silico studies of 4-Anilino Quinazoline derivatives as Anti-tubercular Agents

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i4.3948 ◽

2020 ◽

Vol 11 (4) ◽

pp. 7468-7475

Author(s):

Hemalatha K ◽

Sujatha K ◽

Panneerselvam P ◽

Girija K

Keyword(s):

Mycobacterium Tuberculosis ◽

Molecular Docking ◽

Resistant Strain ◽

In Silico ◽

Research Work ◽

Docking Study ◽

Molecular Docking Study ◽

In Silico Studies ◽

Quinazoline Derivatives ◽

Mycobacterial Cell Wall

Inh A, the Enoyl Acyl Carrier protein Reductase from Mycobacterium tuberculosis is one of the pivotal enzyme involved in the mycobacterial fatty acid elongation cycle and has been considered as an important target for anti-tubercular screening. Inhibition of Inh A affects the biosynthesis of the mycolic acids, which are the central constituents of the mycobacterial cell wall. In the present research work, 4-anilino quinazoline derivatives were designed based on the quinazoline based drugs by means of lipophilic insertion and Fragment replacement. The designed compounds were synthesized, and molecular docking studies were performed on the human pathogenic bacterial enzyme InhA from its parent domain Mycobacterium Tuberculosis. Molecular docking study revealed that compounds SMOQ2, SNAQ3, 4AAQ7, 2AP9, PABAQ10 were found to possess good binding affinity towards the target InhA. With reference to the binding energy obtained from molecular docking study, five compounds were subjected to in vitro anti-tubercular activity against M. tuberculosis H37Rv and I2487 (Resistant strain) using BACTEC MGIT method. Compound SMOQ2 and 4AAQ7 showed sensitivity in both H37Rv (Sensitive strain) and I2487 (Resistant strain) at the concentration of 250, 500, 1000 and 1500 mcg/mL. In silico Pharmacokinetic predictions of the synthesized compounds were determined using SwissADME online web tool. All the synthesized compounds obeyed the Lipinski's rule of five properties.

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