In silico Assessment of Pharmacological Profile of Low Molecular Weight Oligo-Hydroxyalkanoates

Abstract

Polyhydroxyalkanoates (PHAs) are a large class of polyesters that are biosynthesized by microorganisms at large molecular weights (Mw > 80 kDa) and have a great potential for medical applications because of their recognized biocompatibility. Among PHAs, poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxyvalerate), poly(4-hydroxyvalerate), and their copolymers are proposed to be used in biomedicine, but only poly(4-hydroxybutyrate) has been certified for medical application. Along with the hydrolysis of these polymers, low molecular weight oligomers are released typically. In this study, we have used a computational approach to assess the absorption, distribution, metabolism, and excretion (ADME)-Tox profiles of low molecular weight oligomers (≤32 units) consisting of 3-hydroxybutyrate, 4-hydroxybutyrate, 3-hydroxyvalerate, 4-hydroxyvalerate, 3-hydroxybutyrate-co-3-hydroxyvalerate, and the hypothetical PHA consisting of 4-hydroxybutyrate-co-4-hydroxyvalerate. According to our simulations, these oligomers do not show cardiotoxicity, hepatotoxicity, carcinogenicity or mutagenicity, and are neither substrates nor inhibitors of the cytochromes involved in the xenobiotic’s metabolism. They also do not affect the human organic cation transporter 2 (OCT2). However, they are considered to be inhibitors of the organic anion transporters OATP1B1, and OATP1B3. In addition, they may produce eye irritation, and corrosion, skin irritation and have a low antagonistic effect on the androgen receptor.