Details of the cooperative binding of piperlongumine with rat serum albumin obtained by spectroscopic and computational analyses

Author(s)

Ribeiro Povinelli, Ana Paula ^[1] ; Zazeri, Gabriel ^[1] ; Lima, Marcelo de Freitas ^[2] ; Cornelio, Marinonio Lopes ^[1]

Affiliation

^[1] UNESP, Inst Biociencias Letras & Ciencias Exatas IBILCE, Dept Fis, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] UNESP, Inst Biociencias Letras & Ciencias Exatas IBILCE, Dept Quim, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, OCT 30 2019.
• Web of Science Citations: 0

Abstract

Piperlongumine (PPL) has presented a variety of important pharmacological activities. In recent pharmacokinetics studies in rats, this molecule reached 76.39% of bioavailability. Although PPL is present in the bloodstream, no information is found on the interaction between PPL and rat serum albumin (RSA), the most abundant protein with the function of transporting endo/exogenous molecules. In this sense, the present study elucidated the mechanism of interaction between PPL and RSA, using in conjunction spectroscopic and computational techniques. This paper shows the importance of applying inner filter correction over the entire fluorescence spectrum prior to any conclusion regarding changes in the polarity of the fluorophore microenvironment, also demonstrates the convergence of the results obtained from the treatment of fluorescence data using the area below the spectrum curve and the intensity in a single wavelength. Thermodynamic parameters revealed that PPL binds to RSA spontaneously (Delta G < 0) and the process is entropically driven. Interaction density function method (IDF) indicated that PPL accessed two cooperative sites in RSA, with moderate binding constants (2.3 x 10(5) M-1 and 1.3 x 10(5) M-1). The molecular docking described the microenvironment of the interaction sites, rich in apolar residues. The stability of the RSA-PPL complex was checked by molecular dynamics. (AU)

• FAPESP's process: 17/08834-9 - Experimental and computational assays on molecular targets with pharmacological importance and interactions with natural products
• Grantee: Marinônio Lopes Cornélio
• Support Opportunities: Regular Research Grants