Synthesis, Antibacterial Evaluation, and Computational Studies of a Diverse Set of Linezolid Conjugates

The development of new antibiotics to treat multidrug-resistant (MDR) bacteria or possess broad-spectrum activity is one of the challenging tasks. Unfortunately, there are not many new antibiotics in clinical trials. So, the molecular hybridization approach could be an effective strategy to develop...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-02, Vol.15 (2), p.191
Main Authors: Bokhtia, Riham M, Girgis, Adel S, Ibrahim, Tarek S, Rasslan, Fatma, Nossier, Eman S, Barghash, Reham F, Sakhuja, Rajeev, Abdel-Aal, Eatedal H, Panda, Siva S, Al-Mahmoudy, Amany M M
Format: Article
Language:English
Subjects:
Amino acids
antibacterial
Antibiotics
Antimicrobial agents
Bacteria
Chemistry
Chromatography
conjugates
Drug resistance
FDA approval
Gram-negative bacteria
Gram-positive bacteria
linezolid
Pathogens
pharmacophore
QSAR
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Summary:The development of new antibiotics to treat multidrug-resistant (MDR) bacteria or possess broad-spectrum activity is one of the challenging tasks. Unfortunately, there are not many new antibiotics in clinical trials. So, the molecular hybridization approach could be an effective strategy to develop potential drug candidates using the known scaffolds. We synthesized a total of 31 diverse linezolid conjugates , , , , , , and using our established benzotriazole chemistry with good yield and purity. Some of the synthesized conjugates exhibited promising antibacterial properties against different strains of bacteria. Among all the synthesized compounds, is the most promising antibacterial agent with MIC 4.5 µM against and 2.25 µM against . Using our experimental data pool, we developed a robust QSAR ( = 0.926, 0.935; cvOO = 0.898, 0.915; cvMO = 0.903, 0.916 for the and models, respectively) and 3D-pharmacophore models. We have also determined the drug-like properties of the synthesized conjugates using computational tools. Our findings provide valuable insight into the possible linezolid-based antibiotic drug candidates.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15020191