New N-Alkylated Heterocyclic Compounds as Prospective NDM1 Inhibitors: Investigation of In Vitro and In Silico Properties

Abstract

A new family of pyrazole-based compounds (1–15) was synthesized and characterized using different physicochemical analyses, such as FTIR, UV-Visible, 1H, 13C NMR, and ESI/LC-MS. The compounds were evaluated for their in vitro antifungal and antibacterial activities against several fungal and bacterial strains. The results indicate that some compounds showed excellent antibacterial activity against E. coli, S. aureus, C. freundii, and L. monocytogenes strains. In contrast, none of the compounds had antifungal activity. Molecular electrostatic potential (MEP) map analyses and inductive and mesomeric effect studies were performed to study the relationship between the chemical structure of our compounds and the biological activity. In addition, molecular docking and virtual screening studies were carried out to rationalize the antibacterial findings to characterize the modes of binding of the most active compounds to the active pockets of NDM1 proteins.

Novel acrylamide-pyrazole conjugates: Design, synthesis and antimicrobial evaluation.

“…Heterocyclic ligands based on pyrazoles can have a variety of biological uses. For instance, a number of the compounds have been produced with high efficiency as potential antibacterial or antifungal agents [5]. The pyrazole nucleus existence in various structures results in diversified applications in several fields.…”

Synthesis of novel pyrazolone candidates with studying some biological activities and in-silico studies

“…In addition, pyrazole-based heterocyclic ligands have multiple biological applications. For example, many compounds prepared have high efficiencies as antibacterial or antifungal candidates due to their nitrogen electron and proton acceptor abilities 2 . Furthermore, the presence of the pyrazole nucleus in different structures leads to diversified applications in different areas such as technology, medicine, and agriculture.…”

“…With limited facilities to investigate more experimental acceptor abilities, molecular docking became crucial for studying the binding modes and affinities between the prepared compounds and selected biological targets using the lock and key concept 2 . The toxicity predictions and the Lipinski rule of five agreements were determined by POM analysis, one of the well-known approaches to accessing synthetic drugs’ pharmacokinetic properties.…”