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Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug

Liliana P Alarcón1, Yolima Baena2, Rubén H Manzo3

  • 1Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina. lalarcon@fcq.unc.edu.ar.

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This study characterizes DNA-drug interactions, revealing high affinity constants and slow drug release. Some drugs alter DNA

Keywords:
DNAcircular dichroismcomplexationdrug interactionsphysicochemical propertiespolyelectrolytespolymeric drug delivery systems

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Understanding drug interactions with DNA is crucial for drug development and predicting cellular effects.
  • The interaction between DNA phosphate groups and protonated drug species influences drug efficacy and potential side effects.
  • Characterizing these interactions provides a physicochemical basis for drug behavior in biological systems.

Purpose of the Study:

  • To characterize the in vitro interaction between DNA and drugs with basic groups.
  • To determine affinity constants, interaction reversibility, and effects on DNA secondary structure.
  • To explore the potential of DNA-drug complexes in drug delivery and gene transfection.

Main Methods:

  • In vitro characterization of DNA-drug interactions.
  • Determination of affinity constants for counterionic condensation.
  • Analysis of drug release kinetics and circular dichroism profiles of DNA.

Main Results:

  • High affinity constants (order of 10⁶) were observed for DNA-drug complexes.
  • Drug loading decreased the negative electrokinetic potential of DNA.
  • Lipophilic drugs significantly altered DNA secondary structure, while others did not.

Conclusions:

  • The study provides a physicochemical basis for understanding DNA-drug interactions.
  • Findings contribute to identifying drug effects in cell cultures and clinical side effects.
  • The methodology has potential applications in DNA transfection and DNA-based drug delivery.