ADMET properties of novel 5-O-benzoylpinostrobin derivatives

Pratama, Mohammad Rizki Fadhil and Poerwono, Hadi and Siswodiharjo, Siswandono (2019) ADMET properties of novel 5-O-benzoylpinostrobin derivatives. Journal of Basic and Clinical Physiology and Pharmacology, 30 (6). pp. 1-13.

Text 1. Dokumen JBCPP v30s6 2019.pdf Download (250kB)

Abstract

Background: Prediction of the properties of absorption, distribution, metabolism, excretion, and toxicity (AD- MET) from a compound is essential, especially for modified novel compounds. Previous research has suc- cessfully 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 Swis- sADME, 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 pinos- trobin 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.

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