STUDI IN SILICO SENYAWA TURUNAN ANALOG KALKON DAN PIRIMIDIN SEBAGAI ANTIINFLAMASI: PREDIKSI ABSORPSI, DISTRIBUSI, DAN TOKSISITAS

Nursamsiar Nursamsiar, Alprida Tandi Toding, Akbar Awaluddin

Abstract


ABSTRAK

Kalkon merupakan golongan flavonoid yang mempunyai aktivitas biologis seperti antioksidan, antiinflamasi, dan antibakteri. Penelitian ini bertujuan untuk memprediksi profil farmakokinetik (absorpsi dan distribusi) serta toksisitas senyawa turunan analog kalkon dan pirimidin sebagai obat antiinflamasi. Prediksi parameter absorpsi dan distribusi menggunakan perangkat lunak PreADMET® dan sifat toksisitas menggunakan perangkat lunak Toxtree®. Penapisan senyawa berdasarkan kaidah Lipinski menunjukkan bahwa 24 senyawa hasil modifikasi memenuhi kaidah Lipinski, kecuali senyawa 22. Studi prediksi absorpsi dengan parameter HIA (Human Intestinal Absorption) menunjukkan semua senyawa terabsorpsi baik pada usus (70-100%), kecuali senyawa 4, 10, dan 11 moderate absorption (20-70%) dan senyawa 22 kurang terabsorpsi (0-20%). Parameter kemampuan permeabilitas pada sel Caco-2 menunjukkan semua senyawa memiliki kemampuan permeabilitas menengah (4–70%). Sedangkan profil distribusi berdasarkan keterikatan pada protein plasma menunjukkan bahwa semua senyawa terikat lemah pada protein plasma (<90%), kecuali senyawa induk, 3, 5, 7, dan 21 sehingga diprediksi memiliki kemampuan terdistribusi yang kurang baik dalam tubuh. Prediksi toksisitas semua senyawa hasil modifikasi tidak menunjukkan adanya sifat mutagenik maupun karsinogenik.

Kata kunci: absorpsi, distribusi, toksisitas, kalkon.


ABSTRACT

Chalcones are flavonoid compounds that possesing biological activity as antioxidant, anti-inflammatory, and antibacterial. The present study is intended to obtain detail informations of the pharmacokinetic properties (oral, absorption, and distributiion) and toxicity of chalcones and pyrimidines and their analog derivatives using in silico methods. Prediction of their absorption and distribution properties used the PreADMET® software, and toxicity properties used the Toxtree® software. In the chemical screening, 24 designed compounds were in compliance with the Lipinski "rule of fives" and are likely to be reasonably good leads for future drug design, except for compound 22. Prediction studies of the absorption and distribution properties using HIA (Human Intestinal Absorption), plasma protein binding, and permeability against Caco-2 cell parameters show that 24 derived compounds has a middle permeability and the good absorptivity except 4, 10, 11, and 22 compounds have poor absorption properties in the intestine. Meanwhile, distribution profiles based on plasma protein binding show that compounds lead, 3, 5, 7, and 21 are predicted to strongly bind to plasma proteins, and thus are predicted to have poor distribution capabilities in the body. Toxicity prediction of chalcone analogues and pyrimidines derivatives showed that they do not have mutagenic or carsinogenic properties.

Key words: absorption, distribution, toxicity, chalcone.

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DOI: 10.30595/pji.v13i1.891

ISSN: 2579-910X