What is it about?
This article refers to a virtual (in silico) prediction of the similarity, pharmacokinetics and toxicity (ADMET) properties of dimeric acylphloroglucinols from species of Hypericum species native to Central and South America. Their profile was compared to phloroglucinol due to its common moiety, as well as to the hyperforin (a polyisoprenylated acylphloroglucinol from Hypericum perforatum) owing to its well-known antidepressant activity. ADMET properties were predicted with the open source software SwissADME and pk CSM-pharmacokinetics. As far as we know it is the first study on in silico prediction of ADMET properties of these class of compounds.
Featured Image
Why is it important?
Pre-clinical studies have been indicating that dimeric acylphloroglucinol derivatives possesses antidepressant and analgesic properties, and may be promising drug candidates. Therefore, it is relevant to evaluate their pharmacokinetics and toxicity profiles. However, these studies are time-consuming, expensive and present some ethical concerns regarding animal experimentation, which makes its application difficult in the evaluation of a large number of molecules and/or in the early stage of drug development. In this sense, in silico modeling plays a significant role in early pharmaceutical research, especially to estimate ADMET (absorption, distribution, metabolism, excretion and toxicological) properties. The objective of in silico modeling is to predict the in vivo behavior of potential drugs in the human body, bringing together all kinetic processes in a single model. Despite some limitations, the main advantage of in silico prediction is their contribution to reducing costs, time and labor requirements in the drug development pipeline.
Perspectives
Regarding druglikeness properties, we may highlight the following compounds as the highest promising: uliginosin B , isouliginosin and japonicin A. Noteworthy, the study also suggested that dimeric acylphloroglucinols may show some difficulties to cross the blood-brain barrier. Nevertheless, despite of low central nervous system (CNS) penetration predicted, it is important to emphasize that several studies have been published showing the activity of some dimeric acylphloroglucinols in CNS after oral and/or intraperitoneal administration. The predicted toxicity parameters pointed out that most compounds may possess low toxicity, although uliginosin A was predicted as a possible inhibitor of hERG II channel and should be further investigated. In summary, this study corroborates pre-clinical data indicating dimeric acylphloroglucinols as promising drug candidates and point to the need of further pharmacological and medicinal chemistry studies.
Stela Rates
Universidade Federal do Rio Grande do Sul
Read the Original
This page is a summary of: In silico Prediction of ADMET/Drug-likeness Properties of Bioactive
Phloroglucinols from Hypericum Genus, Medicinal Chemistry, December 2023, Bentham Science Publishers,
DOI: 10.2174/1573406419666230601092358.
You can read the full text:
Contributors
The following have contributed to this page
