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.

Computational Assessment of the Pharmacokinetics and Toxicity of the Intensive Sweeteners

“…Information acquired for every investigated sweetener has been synthetized and data are presented in Table I. In order to predict the pharmacokinetics and biological effects of these molecules we have used few accurate computational tools that were extensively used for assessing the biological or side effects of various chemicals: synthetic steroids [34], phthalates [10], oligomers of chitin, chitosan [35] and their derivatives [18], cosmetic ingredients and pesticides [2,16], low molecular weight oligomers of lactic acid [11] and of polydroxyalkanoates [36]. It highlights the applicability of these tools for predicting biological activity and toxicological endpoints for many classes of chemical compounds.…”

Optimization of Culture Conditions for Secretory Production of 3-Hydroxybutyrate Oligomers Using Recombinant Escherichia coli

“…This suggestes that aerobic culture conditions promoted oligomer production rather than P(3HB) accumulation, due to the increased occurrence of CT and alcoholysis reactions. Additionally, since larger size of oligomers were remained in the cells (Hiroe et al, 2021), hydrophobic oligomers trapped in the cell membrane (Roman et al, 2020) may have been pushed out into the extracellular space by vigorous agitation. Based on the result, the agitation speed of 600 rpm was used in the subsequent cultures.…”

In silico Prediction of Skin Sensitization: Quo vadis?

“…These data provide valuable resources for building some in silico models to assess the covert of skin sensitization. In addition, the skin sensitization QSAR models can be applied to not only cosmetic ingredients but also the compound, which can impact the ecosystems such as dye pollution, the effect of personal care products on aquatic species, or plasticizers (Arulanandam et al, 2021;Funar-Timofei and Ilia, 2020;Khan et al, 2020) as well as the pharmacokinetics profiles of low molecular weight oligohydroxyalkanoates (Roman et al, 2020), suggesting that the skin sensitization models has a wide range of applications. To date, most of the published skin sensitization models are qualitative predictions, viz.…”