Generic placeholder image

Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Isatin Derivatives and Their Antiviral Properties Against Arboviruses: A Review

Author(s): Paulo André Teixeira De Moraes Gomes*, Lindomar J. Pena and Ana C. Lima Leite

Volume 19, Issue 1, 2019

Page: [56 - 62] Pages: 7

DOI: 10.2174/1389557518666180424093305

Price: $65


Arboviruses have been spreading rapidly throughout the Western Hemisphere in recent decades. Among the arboviruses with high morbidity and mortality are the members of the Alphavirus and Flavivirus genera. Within the first genus, Chikungunya Virus (CHIKV) is considered one of the most challenging human arboviral infection worldwide, against which there is no specific antivirals. Flaviviruses are some of the main viruses responsible for encephalitis, haemorrhagic disease and developmental defects. Dengue virus (DENV), Japanese Encephalitis Virus (JEV), West Nile Virus (WNV) and Zika Virus (ZIKV) are examples of flaviviruses without clinically approved antiviral agents. Thus, the search for new antivirals becomes highly important. One of the strategies that can be employed to obtain new drugs is the identification and utilization of privileged structures. Isatin is an example of a privileged molecular framework, displaying a broad spectrum of biological activities, including antiviral action. Obtaining and studying the antiviral properties of isatin derivatives have helped to identify important agents with potential activity against different arboviruses. This article reviews some of these isatin derivatives, their structures and antiviral properties reported against this important group of viruses.

Keywords: Arbovirus, Chikungunya virus, Dengue virus, Isatin, Japanese encephalitis virus, West Nile virus, Zika virus.

Graphical Abstract
Fauci, A.S.; Morens, D.M. Zika Virus in the Americas—Yet Another Arbovirus Threat. N. Engl. J. Med., 2016.
Wahid, B.; Ali, A.; Rafique, S.; Idrees, M. Global expansion of chikungunya virus: mapping the 64-year history. Int. J. Infect. Dis., 2017, 58, 69-76.
Rashad, A.A.; Keller, P.A. Structure based design towards the identification of novel binding sites and inhibitors for the Chikungunya virus envelope proteins. J. Mol. Graph. Model., 2013, 44, 241-252.
Jadav, S.S.; Korupolu, P.; Sinha, B.N.; Jayaprakash, V. Chikungunya epidemiological survey and Current available inhibitors. J. Pharmaceut. Chem., 2014, 1(3), 59-67.
Puig-Basagoiti, F.; Tilgner, M.; Forshey, B.M.; Philpott, S.M.; Espina, N.G.; Wentworth, D.E.; Goebel, S.J.; Masters, P.S.; Falgout, B.; Ren, P.; Ferguson, D.M. Triaryl pyrazoline compound inhibits flavivirus RNA replication. Antimicrob. Agents Chemother., 2006, 50(4), 1320-1329.
Solomon, T. Flavivirus encephalitis and other neurological syndromes (Japanese encephalitis, WNV, Tick borne encephalits, Dengue, Zika virus). Int. J. Infect. Dis., 2016, 45, 24.
Daep, C.A.; Muñoz-Jordán, J.L.; Eugenin, E.A. Flaviviruses, an expanding threat in public health: Focus on dengue, West Nile, and Japanese encephalitis virus. J. Neurovirol., 20(6), 539-560.
Li, Z.; Khaliq, M.; Zhou, Z.; Post, C.B.; Kuhn, R.J.; Cushman, M. Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins. J. Med. Chem., 2008, 51(15), 4660-4671.
Bai, F.; Town, T.; Pradhan, D.; Cox, J.; Ledizet, M.; Anderson, J.F.; Flavell, R.A.; Krueger, J.K.; Koski, R.A.; Fikrig, E. Antiviral peptides targeting the west nile virus envelope protein. J. Virol., 2007, 81(4), 2047-2055.
Costantino, L.; Barlocco, D. Privileged structures as leads in medicinal chemistry. Curr. Med. Chem., 2006, 13(1), 65-85.
Cândido-Bacani, P.M.; dos Reis, M.B.; Serpeloni, J.M.; Calvo, T.R.; Vilegas, W.; Varanda, E.A.; Cólus, I.M. Mutagenicity and genotoxicity of isatin in mammalian cells in vivo. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2011, 719(1-2), 47-51.
Ren, A.; Wang, Q.; Fang, Z.; Gao, M.; Wang, H.; Zhang, J.; Xu, W.; Yue, W.; Yin, L.; Liu, Z.; Li, X.; Ding, B. Pharmacokinetic study of isatin in dog plasma by liquid chromatography tandem mass spectrometry. Panminerva Med., 2015, 57(4), 177-182.
Ren, A.; Su, B.; Ye, S.; Wei, X.; Fang, Z.; Wang, Q.; Zhang, J.; Xu, W.; Yue, W.; Yin, L.; Liu, Z.; Li, X.; Ding, B. A pharmacokinetic study of Isatin in Beagles’ bodies. Exp. Ther. Med., 2016, 11(6), 2225-2228.
Vine, K.L.; Matesic, L.; Locke, J.M.; Ranson, M.; Skropeta, D. Cytotoxic and anticancer activities of isatin and its derivatives: A comprehensive review from 2000-2008. Anti-Cancer Agents Med. Chem. (Formerly Curr. Med. Chem.-Anti-Cancer Agents),, 2009, 9(4), 397-414.
Cihan-Üstündağ, G.; Gürsoy, E.; Naesens, L.; Ulusoy-Güzeldemirci, N.; Çapan, G. Synthesis and antiviral properties of novel indole-based thiosemicarbazides and 4-thiazolidinones. Bioorg. Med. Chem., 2016, 24(2), 240-246.
Laursen, S.R.; Jensen, M.T.; Lindhardt, A.T.; Jacobsen, M.F.; Skrydstrup, T. A Palladium-Catalyzed Double Carbonylation Approach to Isatins from 2-Iodoanilines. Eur. J. Org. Chem., 2016, 1881-1885.
Bauer, D.J. Clinical experience with the antiviral drug Marboran® (1-methylisatin 3-thiosemicarbazone). Ann. N. Y. Acad. Sci., 1965, 130(1), 110-117.
Ronen, D.; Nir, E.; Teitz, Y. Effect of N-methylisatin-β-4′: 4′-diethylthiosemicarbazone on intracellular Moloney leukemia virus constituents. Antiviral Res., 1985, 5(4), 249-254.
Teitz, Y.A.; Ronen, D.; Vansover, A.; Stematsky, T.; Riggs, J.L. Inhibition of human immunodeficiency virus by N-methylisatin-β4′: 4′-diethylthiosemicarbazone and N-allylisatin-β-4′: 4′-diallythiosemicarbazone. Antiviral Res., 1994, 24(4), 305-314.
Kang, I.J.; Wang, L.W.; Hsu, T.A.; Yueh, A.; Lee, C.C.; Lee, Y.C.; Lee, C.Y.; Chao, Y.S.; Shih, S.R.; Chern, J.H. Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(7), 1948-1952.
Zhang, H.M.; Dai, H.; Hanson, P.J.; Li, H.; Guo, H.; Ye, X.; Hemida, M.G.; Wang, L.; Tong, Y.; Qiu, Y.; Liu, S. Antiviral activity of an isatin derivative via induction of PERK-Nrf2-mediated suppression of cap-independent translation. ACS Chem. Biol., 2014, 9(4), 1015-1024.
Bauer, D.J.; Apostolov, K. Adenovirus multiplication: Inhibition by methisazone. Science, 1966, 154(3750), 796-797.
Bauer, D.J.; Apostolov, K.; Selway, J.W. Activity of Methisazone against Viruses. Ann. N. Y. Acad. Sci., 1970, 173(1), 314-319.
Teitz, Y.; Ronen, D.; Vasover, A.; Stematsky, T.; Riggs, J.L. Inhibition of human immunodeficiency virus by N-methylisatin-β4′:4′-diethylthiosemicarbazone and N-allylisatin-β-4′:4′-diallythiosemi-carbazone. Antiviral Res., 1994, 305, 314.
Mishra, P.; Kumar, A.; Mamidi, P.; Kumar, S.; Basantray, I.; Saswat, T.; Das, I.; Nayak, T.K.; Chattopadhyay, S.; Subudhi, B.B.; Chattopadhyay, S. Inhibition of chikungunya virus replication by 1- [(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (mbzm-n-ibt). Scientif. Reports, 2016, 6
Rodrigues Faria, N.; Lourenço, J.; Marques de Cerqueira, E.; Maia de Lima, M.; Pybus, O.; Carlos Junior Alcantara, L. Epidemiology of chikungunya virus in bahia, Brazil, 2014-2015. PLOS Curr. Outbreaks,, 2016, Ed(1).
Sebastian, L.; Desai, A.; Shampur, M.N.; Perumal, Y.; Sriram, D.; Vasanthapuram, R. N-methylisatin-beta-thiosemicarbazone derivative (SCH 16) is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo. Virol. J., 2008, 5(1), 64.
Sebastian, L.; Desai, A.; Yogeeswari, P.; Sriram, D.; Madhusudana, S.N.; Ravi, V. Combination of N-methylisatin-β-thiosemicarbazone derivative (SCH16) with ribavirin and mycophenolic acid potentiates the antiviral activity of SCH16 against Japanese encephalitis virus in vitro. Lett. Appl. Microbiol., 2012, 55(3), 234-239.
Minami, M.; Hamaue, N.; Hirafuji, M.; Saito, H.; Hiroshige, T.; Ogata, A.; Tashiro, K.; Parvez, S.H. Isatin, an endogenous MAO inhibitor, and a rat model of Parkinson’s disease induced by the Japanese encephalitis virus.In Oxidative Stress and Neuroprotection; 2006 (pp. 87-95). Springer Vienna.
Blázquez, A.B.; Martín-Acebes, M.A.; Saiz, J.C. Inhibition of west nile virus multiplication in cell culture by Anti-Parkinsonian drugs. Front. Microbiol., 2016, 7.
Gilbert, C.; Bergeron, M.; Méthot, S.; Giguère, J.F.; Tremblay, M.J. Statins could be used to control replication of some viruses, including HIV-1. Viral Immunol., 2005, 18(3), 474-489.
Asenjo, A.; González-Armas, J.C.; Villanueva, N. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating. Virology, 2008, 380(1), 26-33.
Vázquez-Calvo, Á.; Saiz, J.C.; Sobrino, F.; Martín-Acebes, M.A. Inhibition of enveloped virus infection of cultured cells by valproic acid. J. Virol., 2011, 85(3), 1267-1274.
Gastaminza, P.; Whitten-Bauer, C.; Chisari, F.V. Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection. Proc. Natl. Acad. Sci., 2010, 107(1), 291-296.
Zou, B.; Chan, W.L.; Ding, M.; Leong, S.Y.; Nilar, S.; Seah, P.G.; Liu, W.; Karuna, R.; Blasco, F.; Yip, A.; Chao, A. Lead optimization of spiropyrazolopyridones: a new and potent class of dengue virus inhibitors. ACS Med. Chem. Lett., 2015, 6(3), 344-348.
Padmanabhan, P.; Khaleefathullah, S.; Kaveri, K.; Palani, G.; Ramanathan, G.; Thennarasu, S.; Tirichurapalli Sivagnanam, U. Antiviral activity of Thiosemicarbazones derived from α-amino acids against Dengue virus. J. Med. Virol., 2017, 89(3), 546-552.
Zhang, X.G.; Mason, P.W.; Dubovi, E.J.; Xu, X.; Bourne, N.; Renshaw, R.W.; Block, T.M.; Birk, A.V. Antiviral activity of geneticin against dengue virus. Antiviral Res., 2009, 83(1), 21-27.
Wu, R.; Smidansky, E.D.; Oh, H.S.; Takhampunya, R.; Padmanabhan, R.; Cameron, C.E.; Peterson, B.R. Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses. J. Med. Chem., 2010, 53(22), 7958-7966.
Muller, V.D.; Soares, R.O.; dos Santos-Junior, N.N.; Trabuco, A.C.; Cintra, A.C.; Figueiredo, L.T.; Caliri, A.; Sampaio, S.V.; Aquino, V.H. Phospholipase A 2 Isolated from the Venom of crotalus durissus terrificus inactivates dengue virus and other enveloped viruses by disrupting the viral envelope. PLoS One, 2014, 9(11), e112351.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy