3-Methoxyazetidin-2-one Functionalized CuO–CB Microfibrils: A Drug Formulation with Controlled Release and Enhanced Synergistic Antibacterial Activities

Abstract

trans-1-(4′-Methoxyphenyl)-3-methoxy-4-phenyl 3-methoxyazetidin-2-one (or 3-methoxyazetidin-2-one) is one of the important β-lactam derivatives with an ample range of bacterial activities yet few restrictions. To enhance the competency of the chosen 3-methoxyazetidin-2-one, microfibrils composed of copper oxide (CuO) and filter scraps of cigarette butts (CB) were chosen in the current work for developing a potential release formulation. The preparation of CuO-CB microfibrils required a simple reflux technique and a subsequent calcination treatment. The loading of 3-methoxyazetidin-2-one was processed via controlled magnetic stirring followed by centrifugation with microfibrils of CuO-CB. To confirm the loading efficiency, the 3methoxyazetidin-2-one@CuO-CB complex was analyzed by scanning electron microscopy, transmission electron microscopy, and infrared spectroscopy. Compared to the CuO nanoparticles, the release profile of CuO-CB microfibrils indicates only 32% of the drug release in the first 1 h at pH 7.4. As a model organism, E. coli has been utilized for in vitro drug release dynamic studies. Based on the observed drug release data, it was found that the prepared formulation evades premature drug release and triggers the on-demand release of drug inside bacterial cells. The controlled drug release by 3-methoxyazetidin-2-one@CuO-CB microfibrils over a period of 12 h further ascertained the excellent bactericide delivery mechanism to combat deadly bacterial resistance. Indeed, this study provides a strategy to combat antimicrobial resistance and eradicate bacterial disease via nanotherapeutics.

Aroyl-isothiocyanates/isoselenocyanates as precursors to obtain novel cis-3-aroyl-thiourea/urea-β-lactams: design, synthesis, docking and biological evaluation

“…2). 26–32 We initially considered a strategy for synthesizing 3-aroyl-thiourea derivatives by coupling aroyl isothiocyanates with 3-amino-β-lactams. However, the extended reaction times and additional synthetic steps required to obtain 3-urea-β-lactams using the Liptrot method prompted us to explore alternative approaches.…”