Isatin-pyrimidine hybrid derivatives as enoyl acyl carrier protein reductase (InhA) inhibitors against Mycobacterium tuberculosis

Authors

Amira Khalil, Department of Pharmaceutical Chemistry- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo 11837, EgyptFollow
Samy Mohamady, Department of Pharmaceutical Chemistry- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo 11837, Egypt
Amgad Albohy, Department of Pharmaceutical Chemistry- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo 11837, Egypt
Marwa M. Abdel-Aziz, The Regional Center for Mycology & Biotechnology, Al-Azhar University, Cairo, Egypt
Abdalrahman Khalifa, Department of Chemistry, Prairie View A&M University, Prairie View, TX 77446, USA

Document Type

Article

Publication Date

9-1-2023

Abstract

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and 3.9 µg/mL, respectively). Molecular docking studies suggest that this compound binds through the use of relatively unexplored hydrophobic pocket in the active site. Molecular dynamics was used to investigate and support the stability of 4l complex with the target enzyme. This study paves the way for the design and synthesis of novel antitubercular drugs.

Recommended Citation

Khalil, Amira; Mohamady, Samy; Albohy, Amgad; Abdel-Aziz, Marwa M.; and Khalifa, Abdalrahman, "Isatin-pyrimidine hybrid derivatives as enoyl acyl carrier protein reductase (InhA) inhibitors against Mycobacterium tuberculosis" (2023). Pharmacy. 605.
https://buescholar.bue.edu.eg/pharmacy/605