ANALISIS SIFAT FISIKOKIMIA, FARMAKOKINETIK DAN TOKSIKOLOGI PADA PERICARPIUM PALA (Myristica fragransa) SECARA ARTIFICIAL INTELLIGENCE - Abdullah, Surya Sumantri; Putra, Purnawan Pontana; Antasionasti, Irma; Rundengan, Gerald; Suoth, Elly Juliana; Abdullah, Rezky Putri Indarwati; Abdullah, Fatamorgana (Sam Ratulangi University, 2021)
Pala (Myristica fragransa) mengandung senyawa metabolit sekunder yang menunjukkan aktivitas farmakologi. Namun, bagian perikarpium terutama bagian nonvolatil belum banyak dilaporkan. Tujuan dari penelitian ini sebagai screening awal dengan melihat potensi dari senyawa yang dihasilkan perikarpium pala.Dua belas senyawa digambar dua dimensi, dianalisis menggunakan software dan server prediktor. Software yang digunakan adalah Marvin Sketch, ChembioDraw kemudian dianalisis sifat fisikokimia senyawa tersebut. Selanjutnya, server predictor untuk melihat karakteristik farmakokinetika dan toksisitasnya. Berdasarkan analisis sifat fisikokimia senyawa terbaik yaitu licarin (titik didih, titik kritis temperature dan refraksi molar), guaiacin (titik leleh), dan virolane (titik kritis tekanan). Hasil analisis Lipinski menunjukkan senyawa stigmasterol dan b-sitosterol tidak memenuhi kriteria Lipinski.. Selain itu data farmakokinetika menunjukkan stigmasterol, b-sitosterol, asetoneoglinan memiliki kelarutan dalam air yang rendah. Nilai permeabilitas CaCO-2 dan intestinal absorption semuanya memenuhi. Licarin termasuk substrat P-glikoprotein. Volume Distribusi menunjukkan semua senyawa terikat protein serum. b-sitosterol permeabilitas terhadap sawar darah-otak yang paling baik dan erythro-(7S,8R)-∆8’-7-acetoxy-3,4,3’,5’-tetramethoxy-8-O-4’-neolignan permeabilitasnya buruk. Surinamensin menunjukkan permeabilitas terhadap sistem saraf pusat yang tidak dapat berpenerasi. Elemicin dan surinamensin tidak dimetabolisme oleh enzim sitokrom CYP3A4. B-sitosterol memiliki klirens paling tinggi. Semua senyawa menunjukkan tingkat toksisitas yang rendah untuk penggunaan kulit (kecuali elemicin) dan tidak toksik bagi hati.ABSTRACT Nutmeg (Myristica fragransa) contains secondary metabolites that exhibit pharmacological activity. However, the pericarpium, especially the nonvolatile part, has not been widely reported. The purpose of this study was as an initial screening by looking at the potential compounds produced by the nutmeg pericarp. Twelve compounds were drawn in two dimensions, analyzed using software and predictor servers. The software used is Marvin Sketch, ChembioDraw and then the physicochemical properties of these compounds are analyzed. Furthermore, the predictor server to see the pharmacokinetic characteristics and toxicity. Based on the analysis of the physicochemical properties of the best compounds, compound licarin (boiling point, critical point of temperature and molar refractivity), guaiacin (melting point), and virolane (critical point of pressure). The results of Lipinski's analysis showed that stigmasterol and b-sitosterol compounds did not meet Lipinski's rule. In addition, pharmacokinetic data showed that stigmasterol, b-sitosterol, acetoneoglinan had low solubility in the water. The values of CaCO-2 permeability and intestinal absorption were all satisfactory. Licarin is a P-glycoprotein substrate. The Volume Distribution shows all the compositions of the serum proteins. B-sitosterol with the best permeability to the blood-brain barrier and erythro-(7S,8R)-∆8'-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan bad permeability. Surinamensin exhibits permeability to the non-permeable central nervous system. Elemicin and surinamensin are not metabolized by the cytochrome enzyme CYP3A4. B-sitosterol has the highest clearance. All compounds show a low level of toxicity for skin use (except elemicin) and are not toxic to the liver.