Abstract:
The increasing level of antimicrobial resistance in pathogenic
bacteria, together with the lack of new potential drug scaffolds
in the pipeline, make the problem of infectious diseases a
major public health concern. Thus, in this context, a novel
series of 1,3,4-oxadiazole-substituted thiophenes (4a–m) and
1,2,4-triazole (6a–m) substituted thiophene derivatives were
synthesized. Characterization of all the synthesized derivatives
was done by various spectroscopic techniques such as 1
HNMR, 13CNMR spectroscopy and mass spectrometry, and evaluated
for antimicrobial activity against various pathological strains
using broth dilution and disc diffusion method. In particular,
compound 6e and 4e exhibited significant inhibitory potential
with MIC ranging from 2–7 μg mL 1 against S. aureus, B. subtilis,
P. aeruginosa and E. coli. Additionally, compound 6e was found
to be highly potent against methicillin resistant S. aureus
(MRSA; MIC=2 μgmL 1
). Molecular docking studies were also
performed to confer the possible mode of action and
association studies indicate the binding of potent active
compound with DHFR enzyme (Ka=2.10×103 M 1
). Further, the
mechanism of action has also been explored by atomic force
microscopy (AFM), which reveals the bacterial cell wall
deformity and cell wall rupturing that may lead to bacteria cell
death. Additionally, in silico ADME prediction study suggested
the drug like properties of active compoun
