Design, development and evaluation of QSAR and molecular modelling of benzothiazole analogues for antibacterial drug discovery

Abstract

The ongoing hunt for novel antimicrobials is necessitated by antibiotic resistance. In the literature, many compounds having a benzothiazole scaffold have been described. They appear effective against Gram(+ve) and Gram(−ve) bacteria, also Mycobacterium tuberculosis. The antimicrobial activity of the benzothiazole analogues employed in this investigation was discovered against various bacterial and fungal species. As a result, the current study tried to characterise the essential structural properties of benzothiazole analogues utilizing theoretically based molecular descriptors byQSAR. QSAR model is developed based on a multiple linear regression(MLR) approach using the first 21 analogues out of 40 analogues. Such validated QSAR model with important descriptors is captured by allowable parameters responsible for producing inhibition of bacterial species. This validated QSAR model was used to predict -log(MIC) by using the next 19 benzothiazole analogues out of 40 analogues. After that, these 19 analogues were utilized to explore maximum inhibitory interactions. The docking predicted that compounds 23, 26, 28, 31, 32, 33, 35, 36, and 40 represent interactions with crucial amino acids, like VAL28, VAL613, ARG32, ARG885, PRO43, ASP612 and ARG47 having binding energies −6.77269, −6.99922, −9.72827, −7.00734, −7.54004, −7.38046, −7.0953 and −6.31578 respectively. The compounds 22, 24, 25, 34, 37 and 39 show interactions with less common amino acids, such as ALA25, TYR149, LYS740, HIS617, HIS80, PRO79, and SER3115 with binding energies −7.9874, −6.22435, −6.51044, −5.83977, −8.97108 and −7.38662 respectively towards the target protein. Thus, compounds 23, 26, 28, 31, 32, 33, 35, 36, and 40 show maximum inhibitory interactions. Thus, it is an attempt to Control bacterial infections caused by E. coli. Thus, it is an attempt to Control bacterial infections caused by E. coli. As a consequence, these seven compounds may be used to combat Escherichia coli (Gram(−ve)) Deoxyribonucleic acid gyrase in the future.