Abstract
A novel type of 2-(un)substituted phenyl-2,3-dihydroquinazolin-4(1H)-one (DQL) derivatives were designed and synthesized to study the impact of halogen substituents on interactions between DQL and human serum albumin (HSA) by comparison methodology. The interactions between DQL and HSA were studied by fluorescence spectroscopy. The intrinsic fluorescence of human serum albumin was quenched by DQL through a static quenching mechanism. Site marker competitive experiments showed that DQL bound to HSA in site II (subdomain IIIA). The binding constants, the numbers of binding sites and the thermodynamic parameters were measured too. The results indicated that the interactions were spontaneous, mainly through hydrophobic forces, and the substitution by halogen atoms in the benzene ring could increase the interactions between DQL and HSA. Furthermore, the binding affinity was enhanced gradually with the increasing of halogen atomic number.
Highlights
Human serum albumin (HSA), the most abundant protein in the circulatory system, has many physiological and pharmacological functions
The results provide a quantitative understanding of halogen substituent effects on DQL-human serum albumin (HSA) interactions to some extent, which could be useful for further design of potential biologically active substituted quinazolinone derivatives
A number of quinazoline derivatives were designed and synthesized in our laboratory for discovering new biological molecules based upon on this versatile skeleton, and the introduction of t-butylacetyl moieties on quinazolines was found to improve their binding to HSA to some extent through hydrophobic action
Summary
Human serum albumin (HSA), the most abundant protein in the circulatory system, has many physiological and pharmacological functions It is responsible for the maintenance of blood pH and contributes to colloid osmotic blood pressure. It is important to investigate the interactions between new compounds and HSA in the early process of drug discovery [8,9]. -4(1H)-one (DQL) derivatives using the synthetic route shown in Scheme 1, and investigated the binding interactions between five DQLs and HSA at three temperatures by fluorescence spectroscopy. The influence of halogen substituent on DQL-HSA interactions was studied under simulated physiological conditions using 2-phenyl-2,3dihydroquinazolin-4(1H)-one as reference compound. The results provide a quantitative understanding of halogen substituent effects on DQL-HSA interactions to some extent, which could be useful for further design of potential biologically active substituted quinazolinone derivatives.
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