Chemical Physics Impact (Dec 2023)
Discovery of new naphthyridine hybrids against enoyl-ACP reductase (inhA) protein target of Mycobacterium tuberculosis: Molecular docking, molecular dynamics simulations studies
Abstract
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and remains a significant global public health concern, with many new cases reported annually. Despite advancements in TB treatment and control, the emergence of drug-resistant strains has presented a considerable challenge to eradication efforts. One crucial area that necessitates further research in antituberculosis is the development of effective treatments for drug-resistant strains, particularly multidrug resistance tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB), and totally drug–resistant tuberculosis (TDR-TB). The limited and often unsatisfactory treatment options available for drug-resistant strains require the exploration of novel drugs and treatment regimens to combat this escalating issue. This study focuses on designing and developing a series of new 1,8-naphthyridine derivatives for their potential antitubercular activity. The compounds were designed and evaluated through in-silico screening using Molinspiration Cheminformatics, Osiris Property Explorer, AdmetSAR, and SwissADME. The initial filtering process identified the top 16 hybrids, which were then subjected to docking using the AutoDock tool. These compounds' binding energies were higher than the standard drug isoniazid, indicating a potentially more substantial interaction with the target. Based on the promising in silico and docking results, further investigations were conducted on the top 3 compounds, namely ST03, ST09, and ST14. To assess the stability and binding energies observed during the initial docking process, molecular dynamics simulations were performed over a 100 ns period. Both the docking and simulation studies consistently demonstrated that the 1,8-naphthyridine hybrid ST09 exhibited stable and efficient binding energies, suggesting its potential as an effective antituberculosis agent.
