Hasil Pencarian  ::  Simpan CSV :: Kembali

"ABSTRACT

Histone Deacetylase (HDAC) enzymes in the human body play an important role in the transcriptional regulation of gene expression. In the last decade, HDAC inhibitors and activators have been explored and have become known as therapeutic agents for many diseases such as osteodystrophy, neurogenerative disorders, cardiomyopathy, cancer, and diabetes. In recent years, the development of HDAC inhibitors or activators to obtain new potent lead compounds has been conducted using in vitro, in vivo, and in silico methods. Some HDAC family inhibitors and activators have been discovered. But some compounds have limitations such as not selectively binding to one of the HDAC variants. Methods: At present, through bioinformation, HDAC family sequences have been revealed, and some in silico methods such as molecular modelling (homology modelling and pharmacophore modelling), virtual screening, and molecular dynamics are widely used to find and develop new potent and selective compounds. Results: The main utilization of molecular modelling in this work is intended to complete the HDAC structure that partially lacks data regarding its amino acid monomer. Virtual screening methods are helpful in finding the best binding affinity of the test compounds. By molecular dynamic simulation, the temperature, time, and pressure can be adjusted to analyze the hydrogen bond. Conclusion: Combining these in silico approaches will be a more effective and efficient solution in finding new lead compounds for HDAC drug discovery research in the future."

"ABSTRACT

Cytochrome P450 isoform 2C9 (CYP2C9) is a main enzyme which metabolizes phenytoin [I]. The inhibition of this enzyme will increase plasma level of phenytoin. Cimetidine is known as drug that inhibits this enzyme, resulting an increased plasma level of phenytoin [2]. Recently, the three dimentional molecular basis of interaction between phenytoin and cimetidine toward CYP2C9 has not been described well yet. The present findings may represent an important advance for understanding interaction CYP2C9 with drugs to predict its toxicity an also metabolism based on structural interaction from docking results. A computational methodology, molecular docking can be used to analyze interaction which exist between ligand and macromolecule. AutoDock is one of the most commonly used methodology, shows the efficiency of scoring function ligand that bound to its active site [3]. So that, it can be used to understand about interaction between phenytoin and cimetidine in CYP2C9. Crystal structure of CYP2C9 complexed with flurbiprofen (PDB ID: 1R90) has resolution 2.00 A. This structure, used in this experiment, has the closed conformational structure and complexed with S-warfarin. Three dimensional structure of phenytoin and cimetidine were minimized, charge were added for docking preparation. Binding of substrate phenytoin in CYP2C9 is stabilized by hidrogen bonds, interaction with cationic residue Argl08, hydrophobic interaction particularly with Phel 14. On the other side, binding of cimetidine inhibitor in CYP2C9 is stabilized by hydrogen bonds with some amino acid residues, including Glu300 which has role as anionic residue, also the exist of hydrophobic interaction. Cimetidine being competitive inhibitor of CYP2C9 at the substrate recognition site of phenytoin. "

"Cytochrome P450 3A4 (CYP3A4) contributes to the metabolism of 50% of drugs used in therapy [l]. Nowadays, the structures of CYP3A4 are available through crystallography technique and these structures show that CYP3A4 has a flexible active site which allows many probabilities of ligand interaction [2]. Nelfinavir, one of the HIV-Protease inhibitors, is a substrate and also an inhibitor of CYP3A4. However, the CYP3A4-mediated metabolism of nelfinavir result in unknown reactive metabolites which then inactivate CYP3A4 [3]. In silica method through molecular docking is used in this research to study the inhibition of CYP3A4 by nelfinavir and to predict the reactive metabolites of nelfinavir that inactivate CYP3A4. The docking result show that nelfinavir fits the CYP3A4 active site with the conformation that coordinates to the forming of M8 metabolite of nelfinavir. The docking result for M8 gives positive binding energy and the docking result for the intermediate metabolite between nelfinavir and M8 indicates that this intermediate metabolite is responsible for the inhibition of CYP3A4 by nelfinavir through mechanism-based inactivation."

"ABSTRACT

Plasmepsin is a prime enzyme in malarial parasite life cycle. Plasmepsins are worked in the hemoglobin degradation inside the food vacuole during the erythrocytic phase. The structures of this enzyme are available through crystallography and show that these structures have an active site which allows many of probabilities of ligand interactions. Xanthone, a compound of active polyphenolic from Garcinia mangastana Linn. and a Xanthone compound which is isolated from Garcinia mangastona Linn. show an inhibition activity to Plasmadium falciparum through the in vitro method. In this research, the molecular docking method is used to study about inhibiton activity of the enzyme. Molecular docking result of Xanthone analogues to plasmepsin shows that more than one hydrogen bond are involved in the inhibition process."

"ABSTRACT

Malaria is one of problematic infectious diseases worldwide. The absence of an effective vaccine and the spread of drug resistant strains of Plasmodium clearly indicate the necessity for the deveploment of new chemotherapeutic agents. Recent method being developed is searching a new drug of antimalarial using in silica screening, or also know as virtual screening. One of enzyme target that important for growth of the malaria parasite is P/asmodium /a/ciparum Enoyl' Acyl Canier Protein Reductase (PfENR). Inhibition of this enzyme cause the fatty acid biosynthesis type ll will be tem1inated. In this research, in silica screening was performed using GOLD softwa,<;_ to find inhibitor candidates of PfENR by using I igands from the natural compound database of Medicinal Plants in Indonesia. On the GOLD software moleculer docking experiments were perfom1ed between ligands and macromolecule target PfENR. This target that has been optimized with residue removal and charges addition. Ligand is expected to be the PfENR inhibitors. Based on the results obtained from the in silico screening there were S inhibitor candidates which expected to be developed as an antimalarials. These compounds \\"ere Kacmpferol 3-rhamnosyl-(1-3)-rhamnosyl- (1-6)­glucoside, Cyanidin 3.5-di-(6-1mlonylglucoside), 8-Hydroxyapigenin 8-(2",4"­disulfatoglucuronidc). Epigallocmechin 3.5.-di-O-gallate, a··;d Querceti.r1 3.4'-dimethyl ether 7-alpha-L- Arabinofuranosyl-(1-6)-glucoside with the GoldScore ranged from 80,63 to I 00,4 I."

"Rem GTPase is a member ofRGK subfamily (Rad, Rem, Rem2, Gem and Kir) found recently. Rem is highly expressed at cardiac muscle.[l] Crystal structure of Rem (2NZJ) unveiled disordered structures of switch I (residue 102-110) and switch II (residue 135-145). These both regions have been acknowledged to be involved in nucleotide binding and GTP hydrolysis . The purpose of this study is to construct Rem GTPase model by using homology modeling method and to analyze the movements of Rem by performing molecular dynamics (MD) simulation. The selected Rem model, model_Rem_6.pdb, was constructed from multiple templates composed of 421P _A (Ras), 2A78_A (RalA), and 2NZJ_A. Furthermore Rem model was used for ten nanoseconds MD simulation provided for GDP, GTP and without ligand system by using GROMACS 3.3.2. The result was observed from visualization point of view, potential energy, RMSD and RMSF factors. MD simulation revealed that switch regions moved more flexible than other regions in the structure and tended to move away from nucleotide binding site, distinct from the movements of Ras switches which had shown interactions occurred within y­phosphate and both switches."

"Ibuprofen merupakan analgesik anti-inflamasi non steroid (AINS). Umumnya, ibuprofen memiliki sifat alir yang buruk karena sifat kohesifnya yang terlalu tinggi. Masalah lainnya dalam memformulasi bahan ini adalah kecenderungan yang tinggi untuk lengket pada cetakan. Disamping itu kekurangan sifat ibuprofen adalah memiliki laju disolusi yang buruk karena struktur hidrophobiknya. Untuk memperbaiki sifat-sifat tersebut dapat dilakukan metode kristalisasi dengan berbagai pelarut. Pada penelitian ini, dilakukan metode kristalisasi dengan cara pendinginan, penguapan dan penambahan air menggunakan pelarut metanol, etanol dan aseton. Dari seluruh hasil kristalisasi dihasilkan kristal berbentuk prisma yang berwarna putih. Metode kristalisasi terpilih yaitu metode pendinginan, lalu kristal yang dihasilkan dikarakterisasi dengan menggunakan Scanning Electron Microscopy (SEM), Difraksi sinar-X (X-ray diffractometry) dan Differential Scanning Calorimetry (DSC). Dari karakterisasi tersebut menunjukkan terjadinya perubahan bentuk kristal hasil kristalisasi terhadap kristal bahan baku ibuprofen. Metode terpilih ini juga menghasilkan serbuk kristal yang bersifat nonkohesif dengan ukuran partikel 710µm, nilai indeks kompresibilitas: IBMD 14.2%, IBED 16.6%, IBAD 17.1%; nilai sudut istirahat: IBMD 28.1º, IBED 29.7º, IBAD 30.1º dan mempunyai angka kelarutan yang lebih tinggi dibandingkan bentuk kristal yang umum digunakan. Dengan dilakukannya penelitian ini, dapat disimpulkan bahwa metode kristalisasi dapat memperbaiki sifat alir, indeks kompresibilitas, dan laju disolusi dari bahan baku ibuprofen."

"Sik.looksigenase merupakan enzim yang mengkonversi asam arakidonat menjadi prostaglandin Prostaglandin yang dihasilkan berperan penting dalam menimbulkan respons inflamasi. Oleh karena itu obat-obat antiinflamasi baru umumnya dikembangk.an berdasarkan aktivitas inhibisi i.iklooksigenase.Ku1kumin, senyawa aktif dari Curcuma longa, dan analog alamiahnya memiliki aktivitas inhibi􀀖i 􀄑iklooksigenase yang teramati secara in vitro dan m vivo pada penelitian sebelumnya Pada penelitian ini, dilakukan pengujian secara in Jili< o melalui penambatan moleku!er menggunakan AutoDock 4 0 untuk mcngamati aktivitas inhibisi siklooks1genasi beberapa analog kurkuminoid sintesis.Dari hasil penambatan molekuler kemudian analog diperingkatkan berdasarkan 􀆱G ikatan dan konst.anta inhibisinya. Ki. Analog yang diuji memili.ki rataan 􀇏G kluster terendah -10,287 kkal/mol dan tertinggi - 9,220 kkal/mol Sedangkan Ki terendah adalah 22,997 nM dan tertinggi adalah 130,744 nM. Daerah pengikuuin substrat yang penting adalah Ser 353, Tyr 355, Tyr 385, dan Trp 387"