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

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Antimicrobial Drug Discovery

Background:

• Pyrazole derivatives are recognized for diverse biological activities.
• The emergence of antibiotic-resistant bacteria necessitates the development of novel antimicrobial agents.
• Understanding structure-activity relationships is crucial for designing effective drug candidates.

Purpose of the Study:

• To synthesize and characterize a novel series of pyrazole-based compounds.
• To evaluate the in vitro antibacterial and antifungal activities of these compounds.
• To investigate the molecular mechanisms underlying their observed biological activities.

Main Methods:

• Synthesis and full physicochemical characterization (FTIR, UV-Vis, NMR, ESI/LC-MS).
• In vitro antimicrobial screening against various bacterial and fungal strains.
• Computational studies including Molecular Electrostatic Potential (MEP) mapping, inductive/mesomeric effect analysis, molecular docking, and virtual screening against NDM1 proteins.

Main Results:

• Compounds 1-15 were successfully synthesized and characterized.
• Several compounds exhibited significant in vitro antibacterial activity against Gram-negative (E. coli, C. freundii) and Gram-positive (S. aureus, L. monocytogenes) bacteria.
• No significant antifungal activity was observed for any synthesized compounds. Docking studies suggested binding to NDM1 protein active sites.

Conclusions:

• The synthesized pyrazole derivatives represent a promising scaffold for developing new antibacterial agents.
• The findings provide insights into the structure-activity relationships and potential molecular targets (NDM1) for antibacterial action.
• Further optimization is warranted to enhance potency and potentially broaden the spectrum of activity.