| Penulis/Author |
PRAJONA MARBUN (1); apt. Arief Rahman Hakim, S.Si., M.Si. (2); apt. Navista Sri Octa Ujiantari, S.Farm., M.Sc., Ph.D. (3); Dr. B.S. Ari Sudarmanto, M.Si. (4); Prof. Dr. apt. Agung Endro Nugroho, S.Si., M.Si. (5) |
| Abstrak/Abstract |
The absorption-distribution-metabolism-excretion (ADME) profile is a crucial parameter that indicatesthe pharmacokinetics of the drug. The pharmacokinetic properties of a drug represent the fate of the drug in thebody. Curcumin is a main compound in turmeric produced by plants of the Curcuma longa species, and has severalpharmacological effects in animal and human clinical studies. However, preclinical and clinical studies have shownthat curcumin has pharmacokinetic limitations such as poor bioavailability and rapid metabolism which restrict itswidespread use. Therefore, various modifications and synthesis of some analogs using curcumin as a leadcompound with variations in the main structure and attached substituents have been carried out to explore thepharmacological effects as drug candidates. One of the widely developed methods is the modification of curcumin'smain structure, specifically the conversion from diketone to mono-ketone.In 1997, 2,5-dibenzylidenecyclopentanone analogs were synthesized and their biological activity were performed. However, there is no furtherinformation related their pharmacokinetic properties. Therefore, those properties were predicted by performingADME calculation in two online servers, ADMETsar 2.0 and ADMETlab 2.0.. By utilizing the online serversADMETsar 2.0, and ADMETLab 2.0 for in-silico screening of pharmacokinetic properties, from the 17compounds, it was found that the variation among pharmacokinetic aspects was observed, either decreasing orincreasing drug likeness properties of 2,5-dibenzylidene cyclopentanone analogs compared to curcumin. Inaddition, the interaction those analogs with protein or enzymes involved during ADME process such as bloodplasma protein (albumin), p-Glycoprotein, and CYP3A4 was evaluated by performing molecular docking.. Thedocking results showed a sufficiently positive correlation with ADME screening outcomes. |
