IN SILICO SCREENING OF ANTIMALARIAL FROM INDONESIAN MEDICINAL PLANTS DATABASE TO PLASMEPSIN TARGET

Eko Aditya Rifai; Hayun Hayun; Arry Yanuar

doi:10.22159/ajpcr.2017.v10s5.23115

Authors

Eko Aditya Rifai Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Hayun Hayun Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Arry Yanuar Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.

DOI:

https://doi.org/10.22159/ajpcr.2017.v10s5.23115

Keywords:

Antimalarial, In silico screening, Indonesian medicinal plants database, Plasmepsin

Abstract

Objective: Malaria is a disease that impacts millions of people annually. Among the enzymes, plasmepsin is the main enzyme in the plasmodium life cycle that degrades hemoglobin during the erythrocytic phase in the food vacuole. Recently, pharmaceutical industries have been trying to develop therapeutic agents that can cure malaria through the discovery of new plasmepsin inhibitor compounds. One of the developing approaches is the in silico method.

Methods: The chosen in silico screening method in this experiment is a structure-based screening using GOLD software and the Indonesian medicinal plants database.

Results: From ten in silico screening runs, three of the compounds always ranked in the top ten. These three compounds are trimyristin, cyanidin 3,5-di-(6-malonylglucoside), and isoscutellarein 4'-methyl ether 8-(6â€-n-butylglucuronide). Another compound that emerged with high frequency is cyanidin 3,5-di-(6-malonylglucoside).

Conclusions: Based on the results obtained from this screening, 11 inhibitor candidates are expected to be developed as antimalarial. These compounds are trimyristin; cyanidin 3,5-di-(6-malonylglucoside); isoscutellarein 4'-methyl ether 8-(6â€-n-butylglucuronide); cyanidin 3-(6â€-malonylglucoside)-5- glucoside; multifloroside; delphinidin 3-(2-rhamnosyl-6-malonylglucoside); delphinidin 3-(6-malonylglucoside)-3',5'-di-(6-p-coumaroylglucoside); cyanidin 3-[6-(6-sinapylglucosyl)-2-xylosylgalactoside; kaempferol 3-glucosyl-(1-3)-rhamnosyl-(1-6)-galactoside; sanggenofuran A; and lycopene with a GOLD score range from 78.4647 to 98.2836. Two of them, Asp34 and Asp214, bind with all residues in the catalytic site of plasmepsin.

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References

Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2002;2(4):209-18. 2. Rosenthal PJ. Plasmodium falciparum: Effects of proteinase inhibitors on globin hydrolysis by cultured malaria parasites. Exp Parasitol 1995;80(2):272-81.

Olson JE, Lee GK, Semenov A, Rosenthal PJ. Antimalarial effects in mice of orally administered peptidyl cysteine protease inhibitors. Bioorg Med Chem 1999;7:633-8.

Boss C, Richard-Bildstein S, Weller T, Fischli W, Meyer S, Binkert C. Inhibitors of the Plasmodium falciparum parasite aspartic protease plasmepsin II as potential antimalarial agents. Curr Med Chem 2003;10(11):883-907.

Salas F, Fichmann J, Lee GK, Scott MD, Rosenthal PJ. Functional expression of falcipain, a Plasmodium falciparum cysteine proteinase, supports its role as a malarial hemoglobinase. Infect Immun 1995;63(6):2120-5.

Shenai BR, Sijwali PS, Singh A, Rosenthal PJ. Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J Biol Chem 2000;275(37):29000-10.

Sijwali PS, Shenai BR, Gut J, Singh A, Rosenthal PJ. Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3. Biochem J 2001;360:481-9.

Eggleson KK, Duffin KL, Goldberg DE. Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. J Biol Chem 1999;274(45):32411-7.

Bhaumik P, Xiao H, Parr CL, Kiso Y, Gustchina A, Yada RY, et al. Crystal structures of the histo-aspartic protease (HAP) from Plasmodium falciparum. J Mol Biol 2009;388(3):520-40.

Francis SE, Gluzman IY, Oksman A, Knickerbocker A, Mueller R, Bryant ML, et al. Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase. EMBO J 1994;13(2):306-17.

Gluzman IY, Francis SE, Oksman A, Smith CE, Duffin KL, Goldberg DE. Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. J Clin Invest 1994;93(4):1602-8.

Dame JB, Reddy GR, Yowell CA, Dunn BM, Kay J, Berry C. Sequence, expression and modeled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum. Mol Biochem Parasitol 1994;64(2):177-90.

Banerjee R, Liu J, Beatty W, Pelosof L, Klemba M, Goldberg DE. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. Proc Natl Acad Sci U S A 2002;99(2):990-5.

Goldberg DE. Hemoglobin Degradation. Curr Top Microbiol Immunol 2005;295:275-91.

Goldberg DE, Slater AF, Beavis R, Chait B, Cerami A, Henderson GB. Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: A catabolic pathway initiated by a specific aspartic protease. J Exp Med 1991;173(4):961-9.

Klemba M, Goldberg DE. Biological roles of proteases in parasitic protozoa. Annu Rev Biochem 2002;71:275-305.

Asojo OA, Afonina E, Gulnik SV, Yu B, Erickson JW, Randad R, et al. Structures of Ser205 mutant plasmepsin II from Plasmodium falciparum at 1.8 A in complex with the inhibitors rs367 and rs370. Acta Crystallogr D Biol Crystallogr 2002;58:2001-8.

Gupta D, Yedidi RS, Varghese S, Kovari LC, Woster PM. Mechanism-based inhibitors of the aspartyl protease plasm II as potential antimalarial agents. J Med Chem 2010;53(10):4234-47.

Departemen Kesehatan Republik Indonesia. Kebijakan Obat Tradisional Nasional Tahun 2007: Keputusan Menteri Kesehatan RI No. 381/MENKES/SK/III/2007. Jakarta: Ditjen Bina Kefarmasian dan Alat Kesehatan Departemen Kesehatan RI; 2007. Available from: http://www.binfar.depkes.go.id/dat/lama/1206328790_Buku%20 Kebijakan%20Obat%20Tradisional%20Nasional%20Tahun%20 2007.pdf.

Yanuar A, Munâ€™im A, Lagho AB, Syahdi RR, Rahmat M, Suhartanto H. Medicinal plants database and three dimensional structure of the chemical compounds from medicinal plants in Indonesia. Int J Comput Sci 2011;8(5):180-3.

Jenwitheesuk E, Horst JA, Rivas KL, Van Voorhis WC, Samudrala R. Novel paradigms for drug discovery: Computational multitarget screening. Trends Pharmacol Sci 2008;29(2):62-71.

Irwin JJ. Community benchmarks for virtual screening. J Comput Aided Mol Des 2008;22(3-4):193-9.

Hartshorn MJ, Verdonk ML, Chessari G, Brewerton SC, Mooij WT, Mortenson PN, et al. Diverse, high-quality test set for the validation of protein-ligand docking performance. J Med Chem 2007;50(4):726-41.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res 2000;28(1):235-42.

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF chimera-a visualization system for exploratory research and analysis. J Comput Chem 2004;25(13):1605-12.

Pedretti A, Mazzolari A, Vistoli G, Vega ZZ. A versatile toolkit for drug design and protein modelling. J Comput Aided Mol Des 2004;18:167-73.

Syahdi RR, Munâ€™im A, Suhartanto H, Yanuar A. Virtual screening of Indonesian herbal database as HIV-1 reverse transcriptase inhibitor. Bioinformation 2012;8(24):1206-10.

Bolton EE, Wang Y, Thiessen PA, Bryant SH. PubChem: Integrated platform of small molecules and biological activities. Annu Rep Comput Chem 2008;4:217-41.

DeLano WL. The PyMOL Molecular Graphics System, Version 0.99. San Carlos, CA: DeLano Scientific; 2002.

Nayak AP, Tiyaboonchai W, Patankar S, Madhusudhan B, Souto EB. Curcuminoids-loaded lipid nanoparticles: Novel approach towards malaria treatment. Colloids Surf B Biointerfaces 2010;81(1):263-73.

Santos-MagalhÃ£es NS, Mosqueira VC. Nanotechnology applied to the treatment of malaria. Adv Drug Deliv Rev 2010;62(4-5):560-75.

Morris JB, Wang ML. Anthocyanin and potential therapeutic traits in Clitoria, Desmodium, Corchorus, Catharanthus, and Hibiscus Species. Acta Hortic 2007;756:381-8.

Kamiya K, Saiki Y, Hama T, Fujimoto Y, Endang H, Umar M, et al. Flavonoid glucuronides from Helicteres isora. Phytochemistry 2001;57(2):297-301.

Lim SS, Kim H, Lee D. In vitro antimalarial activity of flavonoid and chalcones. Bull Korean Chem Soc 2007;28:2495-7.

Liu KC, Yang SL, Roberts MF, Elford BC, Phillipson JD. Antimalarial activity of Artemisia annua flavonoids from whole plants and cell cultures. Plant Cell Rep 1992;11(12):637-40.

Ferreira JF, Luthria DL, Sasaki T, Heyerick A. Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules 2010;15(5):3135-70.