Antibacterial Efficacy of N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide Analogues against Extended-Spectrum-β-Lactamase Producing Clinical Strain of Escherichia coli ST 131

Abstract

Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum β-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a–h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate’s identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a–h) demonstrated the binding pocket residues involved in the active site of the β-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the β-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds.

Facile Synthesis of 5-Bromo-N-Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo-β-Lactamase Producing Klebsiella pneumoniae ST147

“…Additionally, in order to evaluate the efficacy of this stent, we also looked at N, O, and S heterocyclic formamides. Further, we studied the N, O , and S heterocycles carboxamides like 2-aryl-4-chlorophenyl-5-arylthiophene-2-carboxylates 43 N -(4-bromophenyl)furan-2-carboxamide, 37 N -(4-methylpyridin-2-yl) Thiophene-2-Carboxamide 4-bromo- N -(5-methyl-1H-pyrazol-3-yl)benzamide 16 , 44 to study the effectiveness of these scaffolds. The drug is effective against Staphylococcus aureus and Klebsiella pneumoniae , as well as resistant strains of Salmonella enterica, Acinetobacter baumannii, Enterobacter cloacae , and E. coli.…”

Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

“…At the same time, the amides behave as a hydrophilic binding site against bacterial enzyme proteins, which may cause death or make static growth, leading to good inhibitory activity. 36 Further, we studied the N, O, and S heterocycles carboxamides like N-(4-bromophenyl)furan-2-carboxamide, 32 2-aryl-4-chlorophenyl-5-arylthiophene-2-carboxylates 34 4-bromo-N-(5-methyl-1H-pyrazol-3-yl) benzamide, 35 N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide 37 to study the effectiveness of these scaffolds and found effectiveness against different resistant strains of E. coli, A. baumannii, S. enterica, E. cloacae, S. aureus and K. pneumoniae. We found that heterocyclic carboxamides are pivotal in anti-bacterial activities.…”

The Rising Tide of Antibiotic Resistance: A Study on Extended‐Spectrum Beta‐Lactamase and Carbapenem‐Resistant Escherichia coli and Klebsiella pneumoniae

“…The identification of ESBL was established when a discernible increase in the zone of inhibition surrounding the combination disk (including clavulanate) was detected in contrast to the zone surrounding the disk containing only cephalosporin. Producers that satisfied the designated criteria were categorized as ESBL [ 18 ].…”