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ADMET properties of novel 5-O-benzoylpinostrobin derivatives

  • Mohammad Rizki Fadhil Pratama ORCID logo , Hadi Poerwono ORCID logo and Siswandono Siswodiharjo ORCID logo EMAIL logo
Published/Copyright: December 18, 2019
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 30 Issue 6

Abstract

Background

Prediction of the properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET) from a compound is essential, especially for modified novel compounds. Previous research has successfully designed several modified compounds of 5-O-benzoyl derivatives from pinostrobin, a flavanone that has cytotoxic activity. This study aims to describe the properties of ADMET from the 5-O-benzoylpinostrobin derivative.

Methods

Prediction of the properties of ADMET was carried out using three web servers consisting of SwissADME, pkCSM, and ProTox-II. The observed parameters are divided into ADMET parameters.

Results

In general, absorption parameters indicate that the 5-O-benzoylpinostrobin derivative has lower water solubility than the parent pinostrobin. Distribution parameters show mixed results for distribution through the blood-brain barrier. Metabolism parameters showed different results with generally inhibitory activity shown in CYP2C19, CYP2C9, and CYP3A4. The excretion parameters showed a higher total clearance than pinostrobin except in the trifluoromethyl derivative. The toxicity parameters showed both pinostrobin and the 5-O-benzoylpinostrobin derivatives, including the class IV toxicity category with the lowest LD50 value indicated by the nitro derivative of 1500, with the possible target of the androgen receptor and prostaglandin G/H synthase 1.

Conclusions

Overall, the 5-O-benzoylpinostrobin derivative has the predicted ADMET profile that is relatively similar to pinostrobin, with the most noticeable difference being shown in the absorption parameters where all 5-O-benzoylpinostrobin derivatives have lower water solubility than pinostrobin.

Keywords: 5-O-benzoylpinostrobin; ADMET prediction; pinostrobin; toxicity

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors state no conflict of interest.

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Received: 2019-09-05
Accepted: 2019-10-06
Published Online: 2019-12-18

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jbcpp-2019-0251
Keywords for this article
5-O-benzoylpinostrobin; ADMET prediction; pinostrobin; toxicity

Articles in the same Issue

  1. Reviews
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  3. The implementation of a chronic disease management program (Prolanis) in Indonesia: a literature review
  4. Original Articles
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  6. Evaluating current practices and policies in the use of injectable medicines for treating myalgia in a primary care center in Pamekasan, Indonesia
  7. The contemporary role and potential of pharmacist contribution for community health using social media
  8. Evaluation of rational drug use based on World Health Organization prescribing indicators in a primary care center in Pamekasan East Java, Indonesia
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  10. Factors affecting community pharmacist’s service for women with chronic diseases during pregnancy and breastfeeding: application of the Health Belief Model
  11. Overview of therapeutic changes in antiepileptic drugs in adult patients
  12. Exploration of barriers affecting job satisfaction among community pharmacists
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