Design, Synthesis and In Vitro Biological Evaluation of Pyridine, Thiadazole, Benzimidazole and Acetyl Thiophene Analogues as Anti Tubercular Agents Targeting Enzyme Inh A

Title:Design, Synthesis and In Vitro Biological Evaluation of Pyridine, Thiadazole, Benzimidazole and Acetyl Thiophene Analogues as Anti Tubercular Agents Targeting Enzyme Inh A

Volume: 17 Issue: 6

Author(s): Ayyadurai J Suresh, Sivashankar Nandini, Krishnanmurthy Sangeetha, Loganathan S Dhivya and Parakkot R Surya*

Affiliation:

• Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Affiliated to “The Tamil Nadu Dr. M.G.R Medical University” Chennai - 600 003, Tamil, Nadu,India

Keywords: Tuberculosis, Pyridine, Thiadiazole, Benzimidazole, Acetyl thiophene , Schiff bases, Microplate Alamar Blue Assay

Abstract:

Background: Tuberculosis is a chronic infectious disease that affects one-third of the global population. The emergence of Multi-resistant (MDR) strains and high susceptibility of human immunodeficiency virus (HIV) infected persons to the disease forced to develop novel antituberculosis agents and preferably have a novel mechanism of action as to avoid cross-resistant with other agents. A literature survey indicated that Pyridine, Thiadiazole, Benzimidazole and Acetyl thiophene derivatives exhibit various pharmacological activities, including anti-mycobacterial activity.

Methods: Thus, a series of Pyridine, Thiadiazole, Benzimidazole and Acetyl thiophene based molecules were designed and docked against crucial mtb enzyme target InhA (Enoyl Acyl Carrier Protein Reductase) Enzyme. The docked molecules were screened against good docking-score and multiple interactions and opted for synthesis. Synthesized molecules were recrystallized to obtain purity. All the purified compounds were characterized by various spectral analyses and evaluated for antimycobacterial activity against tuberculosis H37RV strain by Microplate Alamar Blue Assay (MABA) method.

Results: The experimental results showed that Schiff bases of Pyridine (Compounds ‘d’) and Benzimidazole derivatives (Compounds ‘i’ ) possess good anti-tubercular activity with an MIC below 1.6 μg /mL. Furthermore, compound ‘e’ of benzimdazole derivative showed good antitubercular activity with an MIC below 6.25 μg /mL, whereas 2 - acetyl thiopene compounds exhibited moderate antitubercular activity below 50μg/mL.

Conclusion: The comparative in vitro and molecular docking study analysis reveals that compared to chalcones of Acetyl thiophene derivatives, Pyridine, Thiadazole and Benzimidazole based Schiff bases exhibited best antitubercular activity.

Cite this article as:

Suresh J Ayyadurai , Nandini Sivashankar , Sangeetha Krishnanmurthy , Dhivya S Loganathan and Surya R Parakkot *, Design, Synthesis and In Vitro Biological Evaluation of Pyridine, Thiadazole, Benzimidazole and Acetyl Thiophene Analogues as Anti Tubercular Agents Targeting Enzyme Inh A, Current Computer-Aided Drug Design 2021; 17 (6) . https://dx.doi.org/10.2174/1573409916666200724152827