Molecular docking-based screening of methicillin-resistant Staphylococcus aureus FEM proteins with FDA-approved drugs.

Antibiotic resistance stands as one of the most significant public health challenges in recent decades. FEM proteins are responsible for the synthesis of pentaglycine cross-bridge, a primary constituent of bacterial peptidoglycan polymer crosslinking during cell wall biosynthesis. Since they are necessary for bacterial survival and antibiotic resistance, they were considered as significant antibacterial targets. We report herein, the virtual screening and selection of FDA-approved drugs and their potent similar molecules as FEM protein inhibitors and analyzed for inhibiting affinity and their ADMET pharmacokinetic properties. This data provide a foundation for the development and optimization of structurally innovative antimicrobial drugs.

Cloning, Purification, and Biophysical Characterization of FemB Protein from Methicillin-Resistant Staphylococcus aureus and Inhibitors Screening.

Methicillin-resistant Staphylococcus aureus has emerged as a leading cause of nosocomial, community acquired infections worldwide. Earlier investigations revealed that mecA-encoded FEM proteins play a role in antimicrobial resistance by developing unique peptidoglycan cross-linking which helps in the formation of protective cell membrane. In view to this, present study focused on expression, purification FEM proteins, and FemB biophysical characterization with the aid of in silico and in vitro approaches. Furthermore, we carried out biological screening assays and identified the novel potent 1,2,3-triazole conjugated 1,3,4-oxadiazole hybrid molecule which could inhibit the MRSA than the proven oxacillin.

Synthesis, antimicrobial and antioxidant activity of triazole, pyrazole containing thiazole derivatives and molecular docking studies on COVID-19.

New series of biologically active triazole and pyrazole compounds containing 2, 4-disubstituted thiazole analogues (12a-l) were synthesized from p-hydroxy benzaldehyde and phenyl hydrazine in excellent yields and purity. All the synthesized compounds were unambiguously identified based on their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS). The final derivatives were evaluated for their in vitro anti-microbial activity after thorough purification. Among all the tested compounds, the compound 12e, 12f and 12 k possess the highest growth inhibitory activity at MIC values of 4.8, 5.1 and 4.0 µg/ml respectively. The antioxidant properties of these compounds demonstrated and revealed remarkable activity compared to the standard antioxidant by using the DPPH free radical-scavenging assay. Moreover, molecular docking studies to evaluate the probable interactions with the catalytic domain of the gram-positive S. aureus topoisomerase IV enzyme may provide new insights for developing these new hybrids as potential antimicrobial agents. The binding affinities of compounds 12a-l were ranging from - 10.0 to - 11.0 kcal/mol with topoisomerase IV enzyme and with COVID-19 main protease binding affinities are ranging from - 8.2 to - 9.3 kcal/mol. These docking studies reveal that the compounds 12a-l could be the best inhibitors for the novel SARS Cov-2 virus and have more future in discovery of potent drug candidates.