In Silico Approach to Identify Potent Bioactive Pyrrole Analogs as Inhibitors against the Mycobacterium tuberculosis Dihydrofolate Reductase Enzyme

Abstract

Background: MtDHFR inhibitors have been demonstrated to be effective in treating patients with both HIV and Mycobacterium tuberculosis. Dihydrofolate reductase enzyme of M. tuberculosis (MtDHFR) to improve the capacity to treat tuberculosis patients is more pertinent Millions of people are at risk of contracting new TB infections every second, getting sick, and dying, and there is still a lack of a clear knowledge of the pathophysiology. Objective: The objective is to create potent therapeutic novel bioactive compounds that function as  dihydrofolate reductase enzyme of M. tuberculosis (MtDHFR, PDB ID: 1DF7) inhibitors using an in-silico drug creation scheme. Methods: The virtual screening tool Auto Dock 1.5.6 was utilized to carry out molecular docking studies on Dihydrofolate reductase enzyme of M. tuberculosis (MtDHFR). Biovia Discovery Studio examined the docked complex of the ligand and protein. Result: We used sixty different compounds for the docking study; the compounds that demonstrated the best interaction and docking score were chosen, and they will be synthesized. The 10 bioactive substances that have the ability to bind to the 1DF7 have docking scores ranging from -8.5 to -10.4 Kcal/mol. Compound 8 was an excellent candidate for enzyme inhibitor (1DF7) that will be further studied in vitro because it was demonstrated to have the highest allowable docking energy (-10.4 Kcal/mol). Conclusion: An excellent candidate for the dihydrofolate reductase enzyme of M. tuberculosis inhibitor (1DF7) is compound 8, whose IUPAC name is S)-N'-((2-hydroxynaphthalen-1-yl)(m-tolyl)methyl)-4-(1H-pyrrol-1-yl) benzohydrazide. It exhibits a high docking affinity, with a binding energy of -10.4 kcal/mol. Using an in-silico drug design approach for tuberculosis, the effectiveness of pyrrole scaffolding as dihydrofolate reductase enzyme of M. tuberculosis (MtDHFR) antagonists in new treatments has been examined.