Structure-Based Drug Design Studies Toward the Discovery of Novel Chalcone Derivatives as Potential Epidermal Growth Factor Receptor (EGFR) Inhibitors

Human Epidermal Growth Factor Receptor-1 (EGFR), a transmembrane tyrosine kinase receptor (RTK), has been associated with several types of cancer, including breast, lung, ovarian, and anal cancers. Thus, the receptor was targeted by a variety of therapeutic approaches for cancer treatments. A series of chalcone derivatives are among the most highly potent and selective inhibitors of EGFR described to date. A series of chalcone derivatives were proposed in this study to investigate the intermolecular interactions in the active site utilizing molecular docking and molecular dynamics simulations. After a careful analysis of docking results, compounds 1a and 1d were chosen for molecular dynamics simulation study. Extensive hydrogen bond analysis throughout 7 ns molecular dynamics simulation revealed the ability of compounds 1a and 1d to retain the essential interactions needed for the inhibition, especially MET 93. Finally, MM-GBSA calculations highlight on the capability of the ligands to bind strongly within the active site with binding energies of −44.04 and −56.6 kcal/mol for compounds 1a and 1d, respectively. Compound 1d showed to have a close binding energy with TAK-285 (−66.17 kcal/mol), which indicates a high chance for compound 1d to exhibit inhibitory activity, thus recommending to synthesis it to test its biological activity. It is anticipated that the findings reported here may provide very useful information for designing effective drugs for the treatment of EGFR-related cancer disease

Impact of COVID-19 pandemic on multidrug resistant gram positive and gram negative pathogens: A systematic review

Background: There is paucity of data describing the impact of COVID-19 pandemic on antimicrobial resistance. This review evaluated the changes in the rate of multidrug resistant gram negative and gram positive bacteria during the COVID-19 pandemic. Methods: A search was conducted in PubMed, Science Direct, and Google Scholar databases to identify eligible studies. Studies that reported the impact of COVID-19 pandemic on carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum beta-lactamase inhibitor (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CPE) were selected. Studies published in English language from the start of COVID-19 pandemic to July 2022 were considered for inclusion. Results: Thirty eligible studies were selected and most of them were from Italy (n = 8), Turkey (n = 3) and Brazil (n = 3). The results indicated changes in the rate of multidrug resistant bacteria, and the changes varied between the studies. Most studies (54.5%) reported increase in MRSA infection/colonization during the pandemic, and the increase ranged from 4.6 to 170.6%. Five studies (55.6%) reported a 6.8–65.1% increase in VRE infection/colonization during the pandemic. A 2.4–58.2% decrease in ESBL E. coli and a 1.8–13.3% reduction in ESBL Klebsiella pneumoniae was observed during the pandemic. For CRAB, most studies (58.3%) reported 1.5–621.6% increase in infection/colonization during the pandemic. Overall, studies showed increase in the rate of CRE infection/colonization during the pandemic. There was a reduction in carbapenem-resistant E. coli during COVID-19 pandemic, and an increase in carbapenem-resistant K. pneumoniae. Most studies (55.6%) showed 10.4 – 40.9% reduction in the rate of CRPA infection during the pandemic. Conclusion: There is an increase in the rate of multidrug resistant gram positive and gram negative bacteria during the COVID-19 pandemic. However, the rate of ESBL-producing Enterobacteriaceae and CRPA has decrease during the pandemic. Both infection prevention and control strategies and antimicrobial stewardship should be strengthen to address the increasing rate of multidrug resistant gram positive and gram negative bacteria

Novel oxazolones incorporated azo dye: Design, synthesis photophysical-DFT aspects and antimicrobial assessments with In-silico and In-vitro surveys

New derivatives of the oxazolone compounds 4(a-j) and (7a-e) containing azo dye moieties have been prepared via the Erlenmeyer reaction of their azo dye precursors. The characterization of all the synthesized compounds was confirmed by the FT-IR, 1HNMR 13CNMR and MS spectroscopic techniques. The UV-visible examination of the new molecules revealed λmax values in the range of 392–464 nm, depending on the coupling component as well as the various substituents of the benzaldehyde derivatives. All the new chromophores demonstrated an acid chromism behavior, which impacted their usage as potential acid sensors. A detailed study of the azo and hydrazo tautomerism of the prepared dyes 3a-c has been executed through the theoretical DFT calculations. Moreover, the energy levels of the FMOs and their energy difference were predicted by the DFT for all the synthesized molecules to be affected by the geometrical isomerism along with the type of the couplers. These data were employed to elucidate the UV–visible spectral measurements. Furthermore, a detailed study of the substituent effect on the UV absorbance has been achieved by the quantitative structural-activity relationship of the prepared compounds 4f-g and 7a-e. The oxazolone azo dyes were evaluated for their in-vitro antifungal and antibacterial activities and displayed potency in comparison with the reference drugs. Furthermore, the in-silico prediction methodology was contemplated for foretelling the physicochemical, drug likeliness, and ADME traits of all the synthesized compounds, where their respective docking scores were contrasted with their biological activity results