Candidate drug molecule-DNA interaction and molecular modelling of candidate drug molecule

Year 2022, , 1547 - 1555, 25.10.2022

Ayça Karasakal , Yelda Yalçın Gürkan , Sülünay Parlar

https://doi.org/10.32322/jhsm.1117781

Abstract

Aim: 1,4-dihydropyridine derivative, 1-(3-phenyl propyl)-4-(2-(2-hydroxybenzylidene) hydrazone)-1,4-dihydropyridine (abbreviated as DHP) was synthesized as potential agent for Alzheimer’s disease which is a progressive neurodegenerative brain disorder affecting millions of elderly people. With this study, the electrochemical properties of DHP were investigated and its interaction with DNA was analyzed by differential pulse voltammetry (DPV) and cyclic voltammetry (CV) measurements. In addition, this study aims to determine degradation mechanism of the DHP molecule by Density-functional theory (DFT) in gas and in aqueous phase.
Material and Method: Experimental conditions such as immobilization time, the effect of the scan rate, concentration, and the effect of pH were optimized. The method was validated according to validation parameters such as range, precision, linearity, limit of detection (LOD), limit of quantitation (LOQ) and inter/intraday.
Results: Linearity study for the calibration curve of DNA and DHP with DPV was calculated in the calibration range 10-100 µg/mL. The LOD and LOQ values were calculated as 3 and 10 µg/mL and intra-day and inter-day repeatability (RSD %) were 1.85 and 3.64 µg/mL, respectively. After the DHP-DNA interaction, the oxidation currents of guanine decreased as a proof of interaction. The activation energy of the most possible path of reaction was calculated, and their thermodynamically most stable state was determined in gas phase.
Conclusion: We developed to improve a sensitive, fast and easy detection process for determination of interaction between DHP and DNA.

Keywords

DNA, candidate drug molecule, DNA-drug interaction, biosensor, DFT

Project Number

NKUBAP.00.GA.19.217

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