Multi-Spectroscopic and Theoretical Analysis on the Interaction between Human Serum Albumin and a Capsaicin Derivative-RPF101.

Otávio Chaves,Micael Cunha,Maurício Tavares,Roberto Parise-Filho,Carlos Sant’Anna,José Netto-Ferreira

doi:10.3390/biom8030078

Abstract

The interaction between the main carrier of endogenous and exogenous compounds in the human bloodstream (human serum albumin, HSA) and a potential anticancer compound (the capsaicin analogue RPF101) was investigated by spectroscopic techniques (circular dichroism, steady-state, time-resolved, and synchronous fluorescence), zeta potential, and computational method (molecular docking). Steady-state and time-resolved fluorescence experiments indicated an association in the ground state between HSA:RPF101. The interaction is moderate, spontaneous (ΔG° < 0), and entropically driven (ΔS° = 0.573 ± 0.069 kJ/molK). This association does not perturb significantly the potential surface of the protein, as well as the secondary structure of the albumin and the microenvironment around tyrosine and tryptophan residues. Competitive binding studies indicated Sudlow’s site I as the main protein pocket and molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces.

Highlights

IntroductionCapsaicin is a major component of red pepper, being reported as a potent anticancer compound [1]
Capsaicin is a major component of red pepper, being reported as a potent anticancer compound [1].due to its intrinsic pungent effect through transient receptors potential vanilloid type 1(TRPV1) [2], to date the therapeutic use of capsaicin is restricted to pain relief by topical application [3].Using strategies of ligand-based drug design, Tavares et al [4] and Damião et al [5] developed a wide number of capsaicin derivatives aiming to enhance their anticancer profile [6,7]
Previous studies have shown that a solution of Human serum albumin (HSA) in phosphate-buffered saline (PBS) has a strong fluorescence emission at 340 nm when excited at 280 nm [24]

Summary

Introduction

Capsaicin is a major component of red pepper, being reported as a potent anticancer compound [1]. Using strategies of ligand-based drug design, Tavares et al [4] and Damião et al [5] developed a wide number of capsaicin derivatives aiming to enhance their anticancer profile [6,7]. Was revealed as a prominent cytotoxic compound, being active against five different breast and skin cancer cell lines, with no associated pungency in vivo [4]. RF101 can induce arrest of the cell cycle at the G2/M phase through a disruption of the microtubule network. It can cause cellular morphologic changes characteristic of apoptosis and a decrease of mitochondrial membrane potential (∆ψm) [4]

Methods

Results

Discussion

Conclusion