Highly biodegradable fluoroquinolone derivatives designed using the 3D-QSAR model and biodegradation pathways...

Area of Science:

• Environmental Chemistry
• Computational Chemistry
• Biotechnology

Background:

• Fluoroquinolones (FQs) are persistent organic pollutants in wastewater.
• Understanding FQ biodegradability is crucial for effective wastewater treatment.
• Phanerochaete chrysosporium's oxidoreductase plays a role in aerobic FQ degradation.

Purpose of the Study:

• To establish a 3D-QSAR model for predicting and enhancing FQ biodegradability.
• To design novel FQ derivatives with improved biodegradability and environmental profiles.
• To investigate the molecular mechanisms underlying enhanced FQ biodegradation.

Main Methods:

• Comparative Molecular Field Analysis (CoMFA) for 3D-QSAR model development.
• Molecular docking simulations of FQs with Phanerochaete chrysosporium oxidoreductase (PDB ID: 1YZP).
• Design and evaluation of 35 FQ derivatives, including genotoxicity, bioconcentration, and photodegradation assessments.
• Molecular dynamics simulations and analysis of microbial degradation pathways.

Main Results:

• A reliable 3D-QSAR model (q²=0.516, r²pred=0.727) identified key structural features for enhancing biodegradability.
• Derivative-15 exhibited a 27.85% increase in biodegradability compared to levofloxacin (LEV), with favorable environmental characteristics.
• Molecular docking and dynamics simulations confirmed enhanced binding affinity of Derivative-15 to the target oxidoreductase due to improved electrostatic interactions.
• Proposed microbial degradation pathways for LEV and Derivative-15 showed a 32.07% reduction in the total energy barrier for Derivative-15.

Conclusions:

• The 3D-QSAR model effectively guides the design of biodegradable FQ derivatives.
• Derivative-15 represents a promising environmentally friendly FQ with significantly enhanced biodegradability.
• Enhanced electrostatic interactions and reduced degradation energy barriers contribute to the improved biodegradability of designed FQ derivatives.