Nucleic acid binding affinity and antioxidant activity of N-m-Tolyl-4-Chlorophenoxyacetohydroxamicacid

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• Hydroxamic acids are a class of organic acids with diverse natural and synthetic origins.
• Understanding their interaction with nucleic acids is crucial for developing new therapeutic agents.

Purpose of the Study:

• To investigate the binding mechanism of N-m-tolyl-4-chlorophenoxyaceto hydroxamic acid with calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA).
• To evaluate the compound's antioxidant properties and its ability to prevent DNA damage.

Main Methods:

• UV-visible spectroscopy, fluorescence emission analysis, and viscometry were employed to study the binding interactions.
• Competitive binding assays with ethidium bromide (EB) were performed.
• Computational simulations using AutoDock4 software were utilized.
• Antioxidant activity was assessed using DPPH-radical scavenging and β-carotene linoleic acid assays.
• Gel electrophoresis was used to evaluate DNA damage prevention.

Main Results:

• Spectroscopic and viscometric data indicate an intercalative binding mode of the hydroxamic acid with ct-DNA and t-RNA.
• The compound effectively displaced EB from nucleic acids and quenched fluorescence.
• Strong binding constants (K_b) and negative binding free energy values were calculated.
• The compound demonstrated significant antioxidant activity and protected DNA from damage.

Conclusions:

• N-m-tolyl-4-chlorophenoxyaceto hydroxamic acid binds to ct-DNA and t-RNA via intercalation.
• The compound possesses promising antioxidant and DNA-protective properties, warranting further investigation for therapeutic applications.