Effect of Zinc(II)-2,4,5-triphenyl-1H-imidazole Complex Against Replication DENV-2 in Vero Cell

Teguh Hari Sucipto, Aswandi Wibrianto, Fahimah Martak, Siti Churrotin, Ilham Harlan Amarullah, Harsasi Setyawati, Puspa Wardhani, Aryati Aryati, Soegeng Soegijanto

= http://dx.doi.org/10.20473/ijtid.v8i3.11776
Abstract views = 585 times | downloads = 344 times


Dengue virus (DENV) is a significant pathogen emerging worldwide as a cause of infectious disease. DENVs are transmitted to humans through female mosquitoes from Aedes aegypti and Aedes albopictus species. Indonesia is one of the largest countries in the world in dengue endemic regions worldwide. Dengue fever was occurred for the first time as an outbreak in Surabaya and Jakarta in 1968. Many efforts have been made to prevent and treat DENV infections, and clinical trials of a number of vaccines are currently underway. Antiviral testing of DENV is an important alternative for drug characterization and development. Complex compounds are formed as a result of metal and organic complex reactions. Complex compounds can be used as an anti-inflammatory, antimicrobial antifungal, antibacterial, antivirus. The Zn2+ ion can be used as an antiviral candidate. The purpose of this project was investigated Zinc(II)-2,4,5-triphenyl-1H-imidazole antiviral compound to be further tested for inhibitory effect on the replication of DENV-2 in cell culture. DENV replication was measured by antiviral activity assay and cytotoxicity assay. The inhibitory activity of Zinc(II)-2,4,5-triphenyl-1H-imidazole complex compound was determined by Viral ToxGloTM Assay. The cytotoxicity of Zinc(II)-2,4,5-triphenyl-1H-imidazole complex compound was determined by CellTiter96® AQuoeus assay. The inhibitory concentration (IC50) of Zinc(II)-2,4,5-triphenyl- 1H-imidazole against dengue virus type-2 was 34.42 μg/ml. The cytotoxic concentration (CC50) of compound against Vero cell was <100 μg/ml. The results of this study demonstrate the antidengue serotype 2 inhibitory activity of investigated Zinc(II)-2,4,5-triphenyl-1H-imidazole complex and its high toxicity in Vero cells. Further studies are not required before investigated Zinc(II)-2,4,5-triphenylimidazole can be applied in the treatment of DENV-2 infections


Zinc (II), complex compound, cytotoxicity, inhibitory activity, DENV-2

Full Text:



Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504–7.

Chi J, Meng L, Zhai X, Guo Y, Pan S, Zhou C, et al. Tanshinon II A attenuates diabetic cardiomyopathy by down-regulation of mTOR/P70S6K signaling pathway. Int J Clin Exp Pathol. 2016;9(12):12297–305.

Woodland DL. Vaccines Against Dengue Virus. Viral Immunol [Internet]. 2015;28(2):75–75. Available from: https://www.liebertpub.com/doi/10.1089/vim.2015.1502

Lim SP, Noble CG, Shi PY. The dengue virus NS5 protein as a target for drug discovery. Antiviral Res [Internet]. 2015;119(April):57–67. Available from: http://dx.doi.org/10.1016/j.antiviral.2015.04.010

Assunção-Miranda I, Cruz-Oliveira C, Neris RLS, Figueiredo CM, Pereira LPS, Rodrigues D, et al. Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX. J Appl Microbiol. 2016;120(3):790–804.

Saudi M, Zmurko J, Kaptein S, Rozenski J, Neyts J, Van Aerschot A. Synthesis and evaluation of imidazole-4,5-and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus. Eur J Med Chem [Internet]. 2014;87:529–39. Available from: http://dx.doi.org/10.1016/j.ejmech.2014.09.062

Ujjinamatada RK, Baier A, Borowski P, Hosmane RS. An analogue of AICAR with dual inhibitory activity against WNV and HCV NTPase/helicase: Synthesis and in vitro screening of 4-carbamoyl-5-(4,6-diamino-2,5-dihydro-1,3,5-triazin-2-yl)imidazole-1- β-d-ribofuranoside. Bioorganic Med Chem Lett. 2007;17(8):2285–8.

Agotegaray MA, Dennehy M, Boeris MA, Grela MA, Burrow RA, Quinzani O V. Therapeutic properties, SOD and catecholase mimetic activities of novel ternary copper(II) complexes of the anti-inflammatory drug Fenoprofen with imidazole and caffeine. Polyhedron [Internet]. 2012;34(1):74–83. Available from: http://dx.doi.org/10.1016/j.poly.2011.12.005

Carcelli M, Mazza P, Pelizzi C, Zani F. Antimicrobial and genotoxic activity of 2,6-diacetylpyridine bis(acylhydrazones) and their complexes with some first transition series metal ions. X-ray crystal structure of a dinuclear copper(II) complex. J Inorg Biochem. 1995;57(1):43–62.

Arjmand F, Mohani B, Ahmad S. Synthesis, antibacterial, antifungal activity and interaction of CT-DNA with a new benzimidazole derived Cu(II) complex. Eur J Med Chem. 2005;40(11):1103–10.

Ranford JD, Sadler PJ, Tocherb DA, Street G, Oaj LWCIH. Cytotoxicity and Antiviral Activity of Transition-metal Salicylato Complexes and Crystal Structure of. J Chem Soc, Dalt Trans. 1993;3393–9.

Sucipto TH, Churrotin S, Setyawati H, Martak F, Mulyatno KC, Amarullah IH, et al. A new copper (II)-imidazole derivative effectively inhibits replication of denv-2 in vero cell. African J Infect Dis. 2018;12(Special Issue 1):116–9.

Sensi SL, Canzoniero LMT, Yu SP, Ying HS, Koh J, Kerchner GA, et al. Садыков_Отрошенко_Курбатов_(Синтезы_Орг_Препаратов_Пиридинового_Ряда)_(1974). 1997;17(24):9554–64.

Ishida T. Antiviral Activities of Zn2+ Ions for Viral Prevention, Replication, Capsid Protein in Intracellular Proliferation of Viruses. World Sci News [Internet]. 2018;97(March):28–50. Available from: http://yadda.icm.edu.pl/yadda/element/bwmeta1.element.psjd-8ab246c3-8e3f-4707-b97f-0c14fa91b094

Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1–2):55–63.

Lv J, Liu T, Cai S, Wang X, Liu L, Wang Y. Synthesis, structure and biological activity of cobalt(II) and copper(II) complexes of valine-derived schiff bases. J Inorg Biochem. 2006;100(11):1888–96.

Martak F, Cahyani NWD, Nugraheni Z V, Utomo WP. Properties and toxicity of cobalt(II) complex with 2,4,5-triphenyl-1h-imidazole ligand. Indones J Chem [Internet]. 2016;16(3):260–7. Available from: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85002759335&doi=10.22146%2Fijc.1147&partnerID=40&md5=bb30e67ee19232caacec030aee50d3ce

Martak F, Herliana N, Yosina SD, Merriana PC, Wahyudi A, Gunawan WH. Synthesis and Toxicity Test of Cobalt (II), Manganese (II) and Copper (II) Complex with 2-Methyl-4, 5-Diphenyl-1H-Immidazole. Indian J Sci Technol [Internet]. 2018;11(7):1–11. Available from: http://www.indjst.org/index.php/indjst/article/view/115356

Martak F, Wahyudi A, Limanto D, Tajudin M, Ali M. Sintesis dan Karakterisasi Senyawa Kompleks Difenil - 1H - Imidazol. 2018;3(2):159–74.

Haraguchi Y, Sakurai H, Hussain S, Anner BM, Hoshino H. Inhibition of HIV-1 infection by zinc group metal compounds. Antiviral Res. 1999;43(2):123–33.

Sucipto TH, Churrotin S, Setyawati H, Kotaki T, Martak F, Soegijanto S. Antiviral Activity of Copper(Ii)Chloride Dihydrate Against Dengue Virus Type-2 in Vero Cell. Indones J Trop Infect Dis [Internet]. 2017;6(4):84. Available from: http://e-journal.unair.ac.id/index.php/IJTID/article/view/3806

Biot C, Castro W, Botté CY, Navarro M. The therapeutic potential of metal-based antimalarial agents: Implications for the mechanism of action. Dalt Trans. 2012;41(21):6335–49.

Sucipto TH, Churrotin S, Setyawati H, Mulyatno KC, Amarullah IH, Ueda S, et al. INHIBITORY ACTIVITY OF COBALT ( II )– MORIN COMPLEX AGAINST THE REPLICATION OF DENGUE VIRUS TYPE 2. 2017;6(6):6–9.

Raut R, Beesetti H, Tyagi P, Khanna I, Jain SK, Jeankumar VU, et al. A small molecule inhibitor of dengue virus type 2 protease inhibits the replication of all four dengue virus serotypes in cell culture. Virol J. 2015;12(1):1–7.


  • There are currently no refbacks.

Copyright (c) 2020 Indonesian Journal of Tropical and Infectious Disease

View My Stats

IJTID Indexed by : 


IJTID (pISSN 2085-1103eISSN 2356-0991is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Lembaga Penyakit Tropis (Institute of Tropical Disease)

Universitas Airlangga

Kampus C Mulyorejo

Surabaya 60115