Low-Molecular Pyrazine-Based DNA Binders: Physicochemical and Antimicrobial Properties

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Molecular Biology

Background:

• Pyrazine derivatives possess diverse biological activities influenced by structural modifications.
• Understanding structure-activity relationships is crucial for developing new therapeutic agents.

Purpose of the Study:

• To elucidate the structure, physicochemical properties, and DNA interaction of 2-chloro-3-hydrazinopyrazine (2Cl3HP).
• To evaluate the cytotoxic potential of 2Cl3HP for potential clinical applications.

Main Methods:

• Density Functional Theory (DFT) calculations (B3LYP/6-311+G**).
• Experimental analysis including potentiometric and spectrophotometric methods.
• Cytotoxicity assays on human dermal keratinocytes.

Main Results:

• 2-chloro-3-hydrazinopyrazine (2Cl3HP) demonstrated the highest affinity for DNA among tested compounds.
• No significant toxicity was observed in human dermal keratinocytes.
• Both theoretical and experimental data confirmed the hydrophilic nature of 2Cl3HP in aqueous solutions.

Conclusions:

• 2Cl3HP exhibits favorable physicochemical and biological properties, including high DNA affinity and low toxicity.
• The findings support the potential clinical utility of 2Cl3HP.
• The combined theoretical and experimental approach validates the methodology for similar pyrazine derivative studies.