DESIGN AND SCREENING OF GALLIC ACID DERIVATIVES AS INHIBITORS OF MALARIAL DIHYDROFOLATE REDUCTASE (DHFR) BY IN SILICO DOCKING

Ade Arsianti; Hendri Astuty; Fadilah; Anton Bahtiar; Hiroki Tanimoto; Kiyomi Kakiuchi

doi:10.22159/ajpcr.2017.v10i2.15712

Authors

Ade Arsianti Faculty of Medicine, University of Indonesia
Hendri Astuty Faculty of Medicine University of Indonesia
Fadilah Faculty of Medicine University of Indonesia
Anton Bahtiar Faculty of Pharmacy University of Indonesia
Hiroki Tanimoto Graduate School of Materials Science,Nara Institute of Science and Technology
Kiyomi Kakiuchi Graduate School of Materials Science,Nara Institute of Science and Technology

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i2.15712

Abstract

Objective: Malaria is an infection disease caused by plasmodium parasite with high prevalence in tropic and subtropic countries. The aim of this work was to design and screening of Â gallic acid derivatives as inhibitors of malarial dihydrofolate reductase (DHFR) by in silico docking.

Methods: The derivatives were designed by expanding the carboxyl group of gallic acid with open-chain moiety of L-threonine-allyl esters, as well as to modify the hydroxy groups on the aromatic ring of gallic acid with methoxyl group in the derivatives. Â In silico approach has been utilized in finding the potential antimalaria of gallic acid derivatives. Fourteen Gallic acid derivatives (compound 2-15) were modeled into 3D structures by Â ACD Labs software. Geometry optimization and minimization of energy 3D structure of gallic acid derivatives as ligands using the MOE software. Â Docking process and amino acid analysis were executed by using MOE software.Â

Results: In silico docking study resulted in the three top-ranked compounds, namely compound 5, 8 and 12. Among those three top-ranked compounds, compound 12 (octyl gallate), exhibited the strongest interaction and greatest inhibitory activity against the receptor of malarial DHFR.

Conclusion Our results clearly demonstrated that compound 12 (octyl gallate) could be developed as a promising candidate forÂ the new anti-malarial agent.Â Â

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References

Olumes P. Guidelines for the Treatment of Malaria. 2nd ed. Switzerland: WHO; 2011.

Croft AM, Jacquerioz FA, Jones KL. Drugs to prevent malaria in travellers: A systematic review of randomized controlled trials. Human Parasitic Diseases 2010;2:1-19.

Margaret C. World Malaria Report. Switzerland: WHO; 2011.

Buletin Jendela Data dan Informasi. Epidemiology of Malaria in INDONESIA. Volume 1. Triwulan I. Ministry of Health Republic of Indonesia, 2011. Available from: http://www.file:///C:/users/user/ downloads/buletin-malaria.pdf.

Indonesia National Malaria Control Program Strategic Plan 2015-2019.Ministry of Health Republic of Indonesia, 2014. Available from: http://www.static1.1.sqspcdn.com/static/f/471029/26502872/1441109745877/ summary+of+national+malaria+control+program+stra tegic+Plan+++

+edas.pdf.

Irianto K. Parasitologi Berbagai Penyakit Yang Mempengaruhi

Kesehatan Manusia. Bandung, Indonesia: Penerbit Yrama Widya; 2009.

Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, et al. Amodiaquine alone, amodiaquine sulfadoxine-pyrimethamine, amodiaquine artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: A four-arm randomised effectiveness trial. Lancet 2005;365(9469):1474-80.

Kaur M, Velmurugan B, Rajamanickam S, Agarwal R, Agarwal C.

Gallic acid, an active constituent of grape seed extract, exhibits anti- proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice. Pharm Res

;26(9):2133-40.

Verma S, Singh A, Mishra A. Gallic acid: Molecular rival of cancer.

Environ Toxicol Pharmacol 2013;35(3):473-85.

You BR, Moon HJ, Han YH, Park WH. Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis. Food Chem Toxicol 2010;48(5):1334-40.

El Babili F, Bouajila J, Souchard JP, Bertrand C, Bellvert F, Fouraste I, et al. Oregano: Chemical analysis and evaluation of its antimalarial, antioxidant, and cytotoxic activities. J Food Sci 2011;76(3):C512-8.

Sannela AR, Messori L, Casini A, Vincieri FF, Bilia AR, Majori G, et al.

Antimalarial properties of green tea. Biol Pharm Bull 2010;31:903-7.

Murphy AD, Lang-Unnasch N. Alternative oxidase inhibitors potentiate the activity of atovaquone against Plasmodium falciparum. Antimicrob Agents Chemother 1999;43(3):651-4.

Kumar TO, Mahadevan KM, Ganapathy PS, Kumara MN. Synthesis and molecular docing study of 2 aryl/heteroaryl-6-chloroquinoline-4-

carboxylic acids with plasmodium LDH receptor. Int J Pharm Pharm

Sci 2014;7(1):431-7.

Pradeep PS, Kumar TO, Prashantha N, Mahadevan KM. Synthesis, in vitro antibacterial toxicity and molecular docking anticancer activity of novel N-[(2-chloroquinolin-3-yl)] methylidene-2-aniline Schiffs bases. Int J Curr Pharm Res 2015;7(3):37-46.

Sharma P, Chetia D. Docking studies on quinine analog for plasmepsin-II

of malarial parasite using bioinformatics tool. Int J Pharm Pharm Sci

inhibitors. Asian J Pharm Clin Res 2015;8(4):45-52.

Ravi L, Ragunathan A. Potential drug targets for aloin and microdontin: An in silico analysis. Asian J Pharm Clin Res 2016;9(2):194-6.

Arsianti A, Fadilah F, Kusmardi K, Tanimoto H, Morimoto T, Kakiuchi K. Design and molecular docking study of antimycin A analogues as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Open J Med Chem 2014;4:79-86.

Fadilah F, Arsianti A, Kusmardi K, Tedjo A. Molecular docking

;5 Suppl 3:681-5.

studies of opened-chain analogues of antimycin A as caspases

Lulu S, Thabitha A, Priya AM, Vino S. Insignt into the molecular interaction of antimalarial compounds as potential chorismate synthase inhibitors of apoptosis in colorectal cancer. Asian J Pharm Clin Res 2016;9(3):350-2.