1st International and 10th National Iranian Conference on Bioinformatics

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Synthesis and spectroscopic characterization of carboxamide ligands: anti-cancer potential validation by in vitro interaction studies with HSA, DFT, molecular docking

Paper ID : 1418-ICB10

Authors:

parisa rezaei *¹, سودابه شکرالهی¹, آریا تجلی¹, احمد امیری²

¹university of tehran

²شیمی معدنی- دانشکده شیمی- دانشگاه تهران

Abstract:

Human serum albumin (HSA) is one of the basic components of blood plasma and it serves as a storage and carrier protein. Understanding and characterizing the interaction of drugs with HSA has attracted great research interests from decades. The nature and importance of these bindings have direct consequence on drug delivery, pharmacokinetics, pharmacodynamics, therapeutic efficacy and drug designing [1,2]. Herein, two carboxamide ligands have been synthesised by the reaction of adenine with picolinic acid (HL1) and adenine with pyrazine-2-carboxylic acid (HL2) and characterised by UV–Vis, FT-IR, 1H-NMR, and Mass spectroscopy. Also, the optimized structures of these ligands have been investigated using the DFT/B3LYP method with the 6–311++G(d,p) basis set. These show the results of the calculations to be in accordance with the experimental ones.
In the current work, we studied the mechanism of interaction between the anticancer drug and carrier protein human serum albumin (HSA) by using a variety of spectroscopic techniques (fluorescence spectroscopy, and circular dichroism (CD) spectroscopy) and computational methods (molecular docking and molecular dynamic simulation). Fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue with excellent binding constant (38.27 mM-1 for HL1). Also considering that the Kq values for these ligands are >2.0 × 1010 M−1 s−1, indicated that the fluorescence of HSA was quenched by ligands with a static quenching mechanism. Computational molecular docking was carried out to investigate the HSA-binding pose of the compounds. the study of molecular docking also indicated that our ligands could strongly bind to the site I (subdomain IA) of HSA. According to the CD results these ligands can bind to the main blood carrier protein (HSA) and change the secondary structure of the protein.

Keywords:

carboxamide; HSA Binding; Molecular Docking; DFT; Circular Dichroism; MTT assay.

Status : Paper Accepted (Poster Presentation)