Spectroscopic, physicochemical, and pharmacokinetic analysis of α,β-amyrin mixture obtained from Protium heptaphyllum (Aubl.) Marchand resin

Abstract

In the present study, the α,β-amyrin mixture was obtained from Protium heptaphyllum resin, and its molecular structure was determined by one- and two-dimensional Nuclear Magnetic Resonance (NMR) techniques and Mass spectroscopy. This natural compound was also characterized by Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), Fourier Transform Raman (FT-Raman), and Ultraviolet-Visible (UV–Vis) spectroscopy. Vibrational wavenumber and wavevector have been predicted using the Density Functional Theory (DFT) calculations, and the comparison with experimental data allowed us to assign the most of the normal modes of this isomeric binary mixture. The absorption wavelengths and oscillator strengths for the three singlet states of this binary mixture were calculated using time-dependent density functional theory (TD-DFT). The electrochemical behavior was also evaluated. The physical-chemical parameters for ionization constant (pKa), partition coefficient (log P), distribution coefficient (log D), solubility coefficient (log S), and Polar Surface Area (PSA) were predicted. The cardiotoxic effect was also evaluated using the Pred-hERG computational tool. Furthermore, the pharmacokinetic behavior of the α-amyrin and β-amyrin molecules was evaluated by studies of absorption, distribution, metabolism and excretion, and toxicity (ADMET). From the study of the physical-chemical properties, it was possible to infer that the α-amyrin and β-amyrin compounds do not possess ionizable groups in physiological environment. They are essentially lipophilic and remain constant between pH 2–14. From the study of the pharmacokinetic properties of AMDE, it was observed that the α-amyrin and β-amyrin had values that suggest low intestinal absorption and do not reach the central nervous system. It was also verified that they present a lower risk of hepatic toxicity by metabolic activation and do not present cardiotoxic risk.