Microban (United States)

An intermolecular addition of acetophenone derivatives to unactivated alkenes was developed through Pd-(II)/amine cooperative catalysis. This dual catalytic system functions by activating the amide-containing alkene via Pd-(II) coordination while simultaneously enhancing the nucleophilicity of the α-carbon of acetophenones through enamine catalysis, thereby facilitating the C-C bond-forming reaction. Five quinoline-based amide derivatives were designed and synthesized to explore their potential as biologically active agents. The synthesized compounds were structurally characterized using the standard NMR technique and subsequently evaluated for their antimicrobial activity against a panel of pathogenic bacterial and fungal strains. The five derivatives exhibited significant inhibitory effects, with minimum inhibitory concentrations (MICs) comparable to or better than those of reference drugs. To gain insight into the molecular basis of their biological activity, molecular docking studies were performed against relevant microbial target enzymes, revealing favorable binding interactions and high docking scores. Furthermore, molecular dynamics (MD) simulations were carried out to assess the stability and conformational behavior of the most active ligand-protein complexes over time, supporting their potential as stable bioactive candidates. In addition, ADMET in silico predictions indicated good drug-likeness, acceptable pharmacokinetic profiles, and low toxicity risk, reinforcing their potential as promising scaffolds for antimicrobial drug development.

The global breakout of COVID-19 and raised death toll has prompted scientists to develop novel drugs capable of inhibiting SARS-CoV-2. Conducting studies on repurposing some FDA-approved glucocorticoids can be a promising prospective for finding a treatment for COVID-19. In addition, the use of anti-inflammatory drugs, such as glucocorticoids, is a pivotal step in the treatment of critical cases of COVID-19, as they can provoke an inflammatory cytokine storm, damaging lungs. In this study, 22 FDA-approved glucocorticoids were identified through in silico (molecular docking) studies as the potential inhibitors of COVID-19's main protease. From tested compounds, ciclesonide 11, dexamethasone 2, betamethasone 1, hydrocortisone 4, fludrocortisone 3, and triamcinolone 8 are suggested as the most potent glucocorticoids active against COVID-19's main protease. Moreover, molecular dynamics simulations followed by the calculations of the binding free energy using MM-GBSA were carried out for the aforementioned promising candidate-screened glucocorticoids. In addition, quantum chemical calculations revealed two electron-rich sites on ciclesonide where binding interactions with the main protease and cleavage of the prodrug to the active metabolite take place. Our results have ramifications for conducting preclinical and clinical studies on promising glucocorticoids to hasten the development of effective therapeutics against COVID-19. Another advantage is that some glucocorticoids can be prioritized over others for the treatment of inflammation accompanying COVID-19.

Preparation of the ETP-PRO loaded B-CN nanocarrier (1) and analysis of the % of ETP and PRO released (2) using the validated HPLC method (3).