S‐Substituted Oxadiazoles: A Multi‐Faceted Approach to Synthesis, Enzyme Inhibition, and Antibacterial Properties

Siddiqui, Sabahat Zahra; Abbasi, Muhammad Athar; Aziz‐ur‐Rehman; Solangi, Mehwish; Ashraf, Muhammad; Khan, Khalid Mohammed

Antibiotic resistance (AR) is one of the most serious global health issues today. Antibiotic abuse in the medical, veterinary, and agricultural industries, including incorrect antibiotic prescribing, overuse in the livestock industry, and poor cleanliness practices in hospitals, all contribute to the emergence of AR. Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. In the present study, S‐substituted derivatives of 5‐(4‐methoxyphenyl)‐1,3,4‐oxadiazole‐2‐thiol (6 a‐p) were synthesized, fully characterized, and assessed for their inhibitory potential against various Gram‐negative and positive bacterial strains. The compounds demonstrated potent inhibition activity against all selected bacterial strains P. aeroginosa (−), E. coli (−), K. pneumonae (−), S. typhi (−), S. aureus (+), and B. subtilis (+) in comparison to standard ciprofloxacin drug. Among the synthesized derivatives, compounds 6 e and 6 o exhibited high selectivity and potency against the S. typhi (−) strain. The library 6 a‐o was also evaluated for in vitro chymotrypsin enzyme inhibitory activity, and all derivatives displayed weak inhibition potential in contrast to standard chymostatin (IC50 = 8.24±0.11 μM). Studies such as this one may aid in designing and discovering potential antibacterial agents for treating various bacterial infections.

ChemistrySelect, 2024, Vol 9, Issue 7

2365-6549

10.1002/slct.202304685