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Computer automated structure evaluation of quinolone antibacterial agents
G Klopman1, O T Macina, M E Levinson
1Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106.
Antimicrobial Agents and Chemotherapy
|November 1, 1987
Summary
The Computer Automated Structure Evaluation (CASE) program identified key molecular fragments in quinolone antibacterials. These fragments are crucial for DNA gyrase inhibition and antibacterial activity against gram-positive and gram-negative bacteria.
Area of Science:
- Medicinal Chemistry
- Computational Chemistry
- Microbiology
Background:
- Quinolone antibacterials are vital for treating bacterial infections.
- Understanding structure-activity relationships is key to developing new antibiotics.
- DNA gyrase is a primary target for quinolone action.
Purpose of the Study:
- To identify molecular fragments in quinolone antibacterials responsible for DNA gyrase inhibition.
- To correlate these fragments with Minimum Inhibitory Concentrations (MICs) against various bacteria.
- To analyze the role of activating-inactivating fragments in biological activity.
Main Methods:
- Utilized the Computer Automated Structure Evaluation (CASE) program for analysis.
- Correlated CASE-identified fragments with experimental data on DNA gyrase inhibition.
- Examined MIC data against gram-positive and gram-negative bacterial strains.
Main Results:
- CASE successfully generated molecular fragments associated with biological activity.
- Identified specific fragments linked to DNA gyrase inhibition.
- Correlated fragment presence with varying levels of antibacterial efficacy.
Conclusions:
- The CASE program effectively identifies structure-activity relationships in quinolones.
- Specific molecular fragments significantly influence DNA gyrase inhibition and antibacterial potency.
- This approach aids in the rational design of novel quinolone antibacterial agents.