In Silico Analysis of the Phytochemical Compounds in Carica papaya Seeds for Optimizing the Inhibitors of HMG-CoA Reductase

: HMG-CoA Reductase, a key enzyme in the cholesterol biosynthesis, catalyzes the conversion of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) into mevalonate. Therefore, this enzyme is the target of the cholesterol-lowering drugs known as statins. Carica papaya seed extract contains phytochemical compounds that are thought to have a cholesterol-lowering effect. The present study was designed to examine the ability of the secondary metabolites of Carica papaya seeds as an antagonist to HMG-CoA reductase using in silico molecular docking. The docking analysis was carried out in PLANTS 1.2 software in which the lowest ChemPLP score, i.e., free energy, was the molecular docking parameter. Seven ligands were docked with HMG-CoA reductase receptor, three of which were benzyl glucosinolate, oleic acid, and glucotropaeolin that had the best ChemPLP scores, namely -90.5491 kcal/mol, -81.7665kcal/mol, and - 85.1919 kcal/mol, respectively. Benzyl glucosinolate formed hydrogen bonds with the active site of the targeted protein. As a conclusion, this compound can inhibit the enzyme HMG-CoA reductase, and it has the potential for anti-hypercholesterolemia .

[1]  Liliana M. Pacureanu,et al.  COX Inhibition Profile and Molecular Docking Studies of Some 2-(Trimethoxyphenyl)-Thiazoles , 2017, Molecules.

[2]  B. Santoso,et al.  Kajian Docking Molekular Pada Binding Site Pocket Dari Flavopiridol Dalam Menghambat Glikogen Fosforilase Menggunakan Pyrx-Autodock-Vina , 2016 .

[3]  Christopher A Lipinski,et al.  Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions. , 2016, Advanced drug delivery reviews.

[4]  Tudor I. Oprea,et al.  BDDCS, the Rule of 5 and drugability. , 2016, Advanced drug delivery reviews.

[5]  Paul D Leeson,et al.  Molecular inflation, attrition and the rule of five. , 2016, Advanced drug delivery reviews.

[6]  Ratih Nur Indah Siregar.  THE EFFECT OF Eugenia polyantha EXTRACT ON LDL CHOLESTEROL , 2015 .

[7]  Fabrizio Giordanetto,et al.  Oral druggable space beyond the rule of 5: insights from drugs and clinical candidates. , 2014, Chemistry & biology.

[8]  R. Adelina.  Molecular Docking Studies of Annomuricin E and Muricapentocin on Antiproliferation Activity , 2014 .

[9]  J. Serina.  Enzymatic inhibitory activity of hydroxycinnamates (HCs): in silico studies , 2014 .

[10]  J. Frisbee,et al.  Hypercholesterolemia and microvascular dysfunction: interventional strategies , 2010, Journal of Inflammation.

[11]  H. Tsujii,et al.  Dietary Karaya Saponin and Rhodobacter capsulatus Exert Hypocholesterolemic Effects by Suppression of Hepatic Cholesterol Synthesis and Promotion of Bile Acid Synthesis in Laying Hens , 2010, Cholesterol.

[12]  Christopher R. Corbeil,et al.  Towards the development of universal, fast and highly accurate docking/scoring methods: a long way to go , 2008, British journal of pharmacology.

[13]  Ajay N. Jain,et al.  Recommendations for evaluation of computational methods , 2008, J. Comput. Aided Mol. Des..

[14]  P. Hawkins,et al.  How to do an evaluation: pitfalls and traps , 2008, J. Comput. Aided Mol. Des..

[15]  Yoshimasa Nakamura,et al.  Papaya seed represents a rich source of biologically active isothiocyanate. , 2007, Journal of agricultural and food chemistry.

[16]  C. Lipinski.  Lead- and drug-like compounds: the rule-of-five revolution. , 2004, Drug discovery today. Technologies.

[17]  J. Bajorath,et al.  Docking and scoring in virtual screening for drug discovery: methods and applications , 2004, Nature Reviews Drug Discovery.

[18]  G. Schneider,et al.  Virtual Screening for Bioactive Molecules , 2000 .

[19]  J. Rodman,et al.  Molecules, morphology, and Dahlgren's expanded order Capparales , 1996 .

[20]  J. Goldstein,et al.  Regulation of the mevalonate pathway , 1990, Nature.

[21]  M. Nakanishi,et al.  Multivalent control of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mevalonate-derived product inhibits translation of mRNA and accelerates degradation of enzyme. , 1988, The Journal of biological chemistry.

[22]  M. Aswad,et al.  KAJIAN BEBERAPA SENYAWA ANTIINFLAMASI : DOCKING TERHADAP SIKLOOKSIGENASE-2 SECARA IN SILICO , 2012 .

[23]  Wimpie I Pangkahila,et al.  Fraksi Heksan dan Fraksi Metanol Ekstrak Biji Pepaya Muda Menghambat Spermatogonia Mencit (Mus Musculus) Jantan , 2010 .

[24]  Gilles Marcou,et al.  Optimizing Fragment and Scaffold Docking by Use of Molecular Interaction Fingerprints , 2007, J. Chem. Inf. Model..

[25]  Christopher,et al.  ORALLY ACTIVE DRUGS: TECHNICAL AND PEOPLE ISSUES , 2003 .

[26]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[27]  Siswandono.  Prinsip-prinsip Rancangan Obat , 1998 .