Physicochemical characteristics and gastrointestinal absorption behaviors of S-propargyl-cysteine, a potential new drug candidate for cardiovascular protection and antitumor treatment

Abstract

1. As a potential new drug candidate for cardiovascular protection and antitumor treatment, the physicochemical properties, gastrointestinal (GI) absorption behaviors and mechanisms of S-propargyl-cysteine (SPRC) were investigated in this study.

2. SPRC exhibited favorable solubility in aqueous media. The log P and log D values were low (≤1.93 ± 0.08). The pK_a in the acidic and basic regions was 2.08 ± 0.02 and 8.72 ± 0.03, respectively. The isoelectric point was 5.40 ± 0.02. SPRC was stable in the rat GI fluids, and showed no obvious adsorption and metabolism in the rat GI tract.

3. SPRC displayed poor gastric absorption and favorable intestinal absorption in the rat in situ GI perfusion model. Absorption rate constants (k_a), hourly absorption percentage (P) and apparent permeability coefficient (P_app) of SPRC in the small intestine were ≥0.77 ± 0.06 h⁻¹, 59.25 ± 4.02% and (7.99 ± 0.88) × 10⁻⁵cm/s, respectively. Absorption of SPRC exhibited a certain dependence on physiological pH and absorption region. Absorption of SPRC was not inhibited by l-methionine and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid.

4. SPRC showed favorable oral absorption. It can be categorized as a BCS class I drug. The membrane pore transport appeared to be one of the predominant absorption modes for SPRC.

• Biopharmaceutics classification system
• dissociation constant
• equilibrium solubility
• gastrointestinal absorption
• partition coefficient
• physicochemical characteristics
• rat in situ perfusion
• S-propargyl-cysteine

Declaration of interest

This work was supported by the National Natural Science Fund of China (Grant 81374051), the Fundamental Research Funds for the Central Universities of China (Grant 20520133531) and the National Science Fund for Distinguished Young Scholars (Grant 30888002). Weimin Cai, Yizhun Zhu and Guo Ma provided the financial support. There are no conflicts of interest for the paper.