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Current Organic Synthesis

Author(s): Narmin Hamaamin Hussen, Shokhan Jamal Hamid, Mohammed Nawzad Sabir, Aso Hameed Hasan*, Sewara Jalal Mohammed and Aras Ahmed Kamal Shali

DOI: 10.2174/1570179420666230510104319

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Novel Penicillin Derivatives Against Selected Multiple-drug Resistant Bacterial Strains: Design, Synthesis, Structural Analysis, In Silico and In Vitro Studies

Page: [684 - 703] Pages: 20

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Abstract

Introduction: The rising numbers of multiple drug-resistant (MDR) pathogens and the consequent antibacterial therapy failure that resulted in severe medical conditions push to illustrate new molecules with extended activity against the resistant strains. In this manner, chemical derivatization of known antibiotics is proposed to save efforts in drug discovery, and penicillins serve as an ideal in this regard.

Methods: Seven synthesized 6-aminopenicillanic acid-imine derivatives (2a-g) were structure elucidated using FT-IR, 1H NMR, 13C NMR, and MS spectroscopy. In silico molecular docking and ADMET studies were made. The analyzed compounds obeyed Lipinski’s rule of five and showed promising in vitro bactericidal potential when assayed against E. coli, E. cloacae, P. aeruginosa, S. aureus, and A. baumannii. MDR strains using disc diffusion and microplate dilution techniques.

Results: The MIC values were 8 to 32 μg/mL with more potency than ampicillin, explained by better membrane penetration and more ligand-protein binding capacity. The 2g entity was active against E. coli. This study was designed to find new active penicillin derivatives against MDR pathogens.

Conclusion: The products showed antibacterial activity against selected MDR species and good PHK, PHD properties, and low predicted toxicity, offering them as future candidates that require further preclinical assays.

Graphical Abstract

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