Interaction Of2-ethy1-3-ary1-quinazolin-4-one With Biological Macromolecules

Bovine serum albumin (BSA), human serum albumin (HSA) and DNA are common biological macromolecules as well as essential substances in the life. They have respective biological function, which is the ability to transport drugs and participate in the metabolism. Study on the interaction between small molecules and these biological macromolecules at the molecular level is of current interest in many research areas such as life science, biology, chemistry and clinical medicine, etc.Quinazolineones have been paid much attention to mainly due to some of their pharmacological and biological activities, including anti-HIV-1activity, anticancer activity, anticonvulsants activity, insect resistance and sterilization, etc. In recent years, some studies showed quinazolineone may possess greater biological activity, with respect to structural modification of quinazolineone. In this paper, two kinds of quinazolineone compounds (3-nitrophenyl-quinazolin-4-one and3-aminophenyl-quin-azolin-4-one) have been designed and synthesized according to related literature. Meanwhile, the interaction of them with bovine serum albumin (BSA), human serum albumin (HSA) and calf thymus DNA (ctDNA) have been investigated using a variety of methods including spectroscopy, electrochemistry and molecular docking. The present work consists of the following several parts:In the first part, new compounds2-ethyl-3-(3-nitrophenyl) quinazolin-4-one (ENPQO) and2-ethyl-3-(3-aminophenyl)quinazolin-4-one(EAPQO) were synthesized and characterized.In the second part, the interaction between ENPQO and BSA/HSA under physiological conditions was studied by using a variety of methods including fluorescence spectroscopy, UV-vis absorbance spectroscopy, fourier transform infrared(FT-IR)spectroscopy, circular dichroism (CD) spectroscopy, electrochemical impedance spectroscopy (EIS) and molecular docking. Spectroscopic analysis of the fluorescence quenching and ultraviolet absorption revealed that the quenching mechanism of BSA/HSA by ENPQO was static quenching procedure. The EIS results showed that ENPQO might bind to BSA/HSA via the formation of the ENPQO-BSA/HSA complex. In addition, the quenching constant, binding constant and binding distance (r) between ENPQO and the tryptophan residue of BSA/HSA were caculated according to correlation formula, the results indicated that the energy transfer from SA to ENPQO occurred with a large probability. The calculated thermodynamic parameters (△H, AS,△G) demonstrated that the action force was mainly hydrophobic force. We also focus on the effect of ENPQO on the conformation of BSA/HSA which were meased by synchronous fluorescence, FT-IR and CD spectra. Molecular docking analysis further identified that ENPQO bound to HSA on site I in subdomain IIA. Moreover, investigation on the interaction between ENPQO and calf thymus DNA (ctDNA) was made by using a variety of methods including fluorescence spectra, UV-vis absorbance spectra, fluorescence polarization, ionic strength effect and molecular modeling. The results indicated that ENPQO might bind to ctDNA via groove binding.In the third part, the binding characteristics and mechanism EAPQO to BSA/HSA have been investigated. The results showed that the quenching of EAPQO to BSA/HSA belongs to static quenching with complex formation.The quenching constant, the binding constant and binding distance were caculated. The action force between EAPQO and BSA/HSA can be estimated accoding to the thermodynamic parameters (△H,△G and△S). The measuring of synchronous fluorescence, FT-IR and CD showed that conformational changes of BSA/HSA could be induced by EAPQO.