| Autor: |
Pratama MRF; Universitas Airlangga, Doctoral Program of Pharmaceutical Science, Faculty of Pharmacy, Kampus C UNAIR, Jl. Dr. Ir. Soekarno Mulyorejo Surabaya, East Java, Indonesia., Poerwono H; Universitas Airlangga, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kampus C UNAIR, Jl. Dr. Ir. Soekarno Mulyorejo Surabaya, East Java, Indonesia., Siswodiharjo S; Universitas Airlangga, Department of Pharmaceutical Chemistry, Faculty of Pharmacy,, Kampus C UNAIR, Jl. Dr. Ir. Soekarno Mulyorejo Surabaya, East Java, Indonesia. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of basic and clinical physiology and pharmacology [J Basic Clin Physiol Pharmacol] 2019 Dec 18; Vol. 30 (6). Date of Electronic Publication: 2019 Dec 18. |
| DOI: |
10.1515/jbcpp-2019-0251 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
