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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Chloroquine Analogs: An Overview of Natural and Synthetic Quinolines as Broad Spectrum Antiviral Agents

Author(s): Veera B. Pallaval, Manasa Kanithi, Sangeetha Meenakshisundaram, Achanta Jagadeesh, Mattareddy Alavala, Thanigaimalai Pillaiyar, Manoj Manickam* and Bojjibabu Chidipi*

Volume 27, Issue 9, 2021

Published on: 11 December, 2020

Page: [1185 - 1193] Pages: 9

DOI: 10.2174/1381612826666201211121721

Price: $65

Abstract

SARS-CoV-2, a positive single-stranded RNA enveloped coronavirus, currently poses a global health threat. Drugs with quinoline scaffolds have been studied to repurpose their useful broad-spectrum properties into treating various diseases, including viruses. Preliminary studies on the quinoline medications, chloroquine and hydroxychloroquine, against SARS-CoV-2, have shown to be a potential area of interest for drug development due to their ability to prevent viral entry, act as anti-inflammatory modulators, and inhibit key enzymes allowing reduced viral infectivity. In addition to Chloroquine and Hydroxychloroquine, we discussed analogs of the drugs to understand the quinoline scaffold’s potential antiviral mechanisms. The heterocyclic scaffold of quinoline can be modified in many ways, primarily through the modification of its substituents. We studied these different synthetic derivatives to understand properties that could enhance its antiviral specificity thoroughly. Chloroquine and its analogs can act on various stages of the viral life cycle, pre and post entry. In this study, we reviewed chloroquine and its synthetic and natural analogs for their antiviral properties in a variety of viruses. Furthermore, we reviewed the compound’s potential abilities to attenuate symptoms associated with viral infections. Natural compounds that share scaffolding to chloroquine can act as antivirals or attenuate symptoms through the stimulation of the host immune system or reduction of oxidative stress. Furthermore, we discuss perspectives of the drug’s repurposing due to its ability to inhibit the beta-hematin formation and to be a Zinc Ionophore.

Keywords: Natural compounds, SARS-CoV-2, quinoline chloroquine, hydroxychloroquine, antivirals, COVID-19.

« Previous Next »
[1]
Wang Z. Clinical Features of 69 Cases With Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis 2020; 71(15): 769-77.
[2]
Mollalo A, Vahedi B, Rivera KM. GIS-based spatial modeling of COVID-19 incidence rate in the continental United States. Sci Total Environ 2020; 728.
[http://dx.doi.org/10.1016/j.scitotenv.2020.138884] [PMID: 32335404]
[3]
Fan S. Research progress on repositioning drugs and specific therapeutic drugs for SARS-CoV-2. Future Med Chem 2020; 12(17): 1565-78.
[4]
Chu CM, Cheng VC, Hung IF, et al. HKU/UCH SARS Study Group. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004; 59(3): 252-6.
[http://dx.doi.org/10.1136/thorax.2003.012658] [PMID: 14985565]
[5]
Cheung TM, Yam LY, So LK, et al. Effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome. Chest 2004; 126(3): 845-50.
[http://dx.doi.org/10.1378/chest.126.3.845] [PMID: 15364765]
[6]
Yang JW, et al. Corticosteroid administration for viral pneumonia: COVID-19 and beyond. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2020; 26(9): 1171-7..
[7]
Veronese N, Demurtas J, Yang L, et al. Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature. Front Med (Lausanne) 2020; 7: 170-0.
[http://dx.doi.org/10.3389/fmed.2020.00170] [PMID: 32391369]
[8]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[9]
Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020; 71(15): 732-9.
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[10]
Ascaso FJ, Rodríguez NA, San Miguel R, Huerva V. The “flying saucer” sign on spectral domain optical coherence tomography in chloroquine retinopathy. Arthritis Rheum 2013; 65(9): 2322.
[http://dx.doi.org/10.1002/art.38063] [PMID: 23817782]
[11]
Bortoli R, Santiago M. Chloroquine ototoxicity. Clin Rheumatol 2007; 26(11): 1809-10.
[http://dx.doi.org/10.1007/s10067-007-0662-6] [PMID: 17594118]
[12]
Bogaczewicz A, Sobow T. Psychiatric adverse effects of chloroquine. Psychiatria i Psychologia Kliniczna 2017; 17: 111-4.
[http://dx.doi.org/10.15557/PiPK.2017.0012]
[13]
Geamănu Pancă A, Popa-Cherecheanu A, Marinescu B, Geamănu CD, Voinea LM. Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. J Med Life 2014; 7(3): 322-6.
[PMID: 25408748]
[14]
Coutinho MB, Duarte I. Hydroxychloroquine ototoxicity in a child with idiopathic pulmonary haemosiderosis. Int J Pediatr Otorhinolaryngol 2002; 62(1): 53-7.
[http://dx.doi.org/10.1016/S0165-5876(01)00592-4] [PMID: 11738695]
[15]
El-Solia A, Al-Otaibi K, Ai-Hwiesh AK. Hydroxychloroquine-induced hypoglycaemia in non-diabetic renal patient on peritoneal dialysis BMJ Case Rep 2018; 2018.
[http://dx.doi.org/10.1136/bcr-2017-223639 ] [PMID: 29669768]
[16]
Vlahopoulos S, Critselis E, Voutsas IF, et al. New use for old drugs? Prospective targets of chloroquines in cancer therapy. Curr Drug Targets 2014; 15(9): 843-51.
[http://dx.doi.org/10.2174/1389450115666140714121514] [PMID: 25023646]
[17]
Sahraei Z, Shabani M, Shokouhi S, Saffaei A. Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine. Int J Antimicrob Agents 2020; 55(4): 105945-5.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105945] [PMID: 32194152]
[18]
Michne VJSWF. (S)-(+)-hydroxychloroquine. United States Patent (US5314894A) 1994.
[19]
William Francis MJS. Use of (S)-(+)-Hydroxychloroquine. European Patent Specification,1993
[20]
Ducharme J, Fieger H, Ducharme MP, Khalil SK, Wainer IW. Enantioselective disposition of hydroxychloroquine after a single oral dose of the racemate to healthy subjects. Br J Clin Pharmacol 1995; 40(2): 127-33.
[http://dx.doi.org/10.1111/j.1365-2125.1995.tb05768.x] [PMID: 8562294]
[21]
D’Acquarica I, Agranat I. Chiral switches of chloroquine and hydroxychloroquine: potential drugs to treat COVID-19. Drug Discov Today 2020; 25(7): 1121-3.
[http://dx.doi.org/10.1016/j.drudis.2020.04.021] [PMID: 32371138]
[22]
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 69-9.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[23]
Mauthe M, Orhon I, Rocchi C, et al. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy 2018; 14(8): 1435-55.
[http://dx.doi.org/10.1080/15548627.2018.1474314] [PMID: 29940786]
[24]
Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 2020; 6: 16.
[http://dx.doi.org/10.1038/s41421-020-0156-0] [PMID: 32194981]
[25]
Delvecchio R, Higa LM, Pezzuto P, et al. Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models. Viruses 2016; 8(12)
[http://dx.doi.org/10.3390/v8120322] [PMID: 27916837]
[26]
Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Chloroquine is a zinc ionophore. PLoS One 2014; 9(10): e109180-0.
[http://dx.doi.org/10.1371/journal.pone.0109180] [PMID: 25271834]
[27]
Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The Role of Zinc in Antiviral Immunity. Adv Nutr 2019; 10(4): 696-710.
[http://dx.doi.org/10.1093/advances/nmz013] [PMID: 31305906]
[28]
Kar M, Khan NA, Panwar A, et al. Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells. Front Immunol 2019; 10: 2347-7.
[http://dx.doi.org/10.3389/fimmu.2019.02347] [PMID: 31632411]
[29]
Fantini J, Di Scala C, Chahinian H, Yahi N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob Agents 2020; 55(5): 105960-0.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105960] [PMID: 32251731]
[30]
Kwiek JJ, Haystead TA, Rudolph J. Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry 2004; 43(15): 4538-47.
[http://dx.doi.org/10.1021/bi035923w] [PMID: 15078100]
[31]
Klumperman J, Locker JK, Meijer A, Horzinek MC, Geuze HJ, Rottier PJ. Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding. J Virol 1994; 68(10): 6523-34.
[http://dx.doi.org/10.1128/JVI.68.10.6523-6534.1994] [PMID: 8083990]
[32]
Seitz M, Valbracht J, Quach J, Lotz M. Gold sodium thiomalate and chloroquine inhibit cytokine production in monocytic THP-1 cells through distinct transcriptional and posttranslational mechanisms. J Clin Immunol 2003; 23(6): 477-84.
[http://dx.doi.org/10.1023/B:JOCI.0000010424.41475.17] [PMID: 15031635]
[33]
Briant L, Robert-Hebmann V, Acquaviva C, Pelchen-Matthews A, Marsh M, Devaux C. The protein tyrosine kinase p56lck is required for triggering NF-kappaB activation upon interaction of human immunodeficiency virus type 1 envelope glycoprotein gp120 with cell surface CD4. J Virol 1998; 72(7): 6207-14.
[http://dx.doi.org/10.1128/JVI.72.7.6207-6214.1998] [PMID: 9621091]
[34]
Kono M, Tatsumi K, Imai AM, Saito K, Kuriyama T, Shirasawa H. Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: involvement of p38 MAPK and ERK. Antiviral Res 2008; 77(2): 150-2.
[http://dx.doi.org/10.1016/j.antiviral.2007.10.011] [PMID: 18055026]
[35]
Zhou D, Dai S-M, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother 2020; 75(7): 1667-70.
[http://dx.doi.org/10.1093/jac/dkaa114] [PMID: 32196083]
[36]
Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 2020; 55(5)
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[37]
Balasubramanian A, Teramoto T, Kulkarni AA, Bhattacharjee AK, Padmanabhan R. Antiviral activities of selected antimalarials against dengue virus type 2 and Zika virus. Antiviral Res 2017; 137: 141-50.
[http://dx.doi.org/10.1016/j.antiviral.2016.11.015] [PMID: 27889529]
[38]
Lane TR, Comer JE, Freiberg AN, Madrid PB, Ekins S. Repurposing Quinacrine against Ebola Virus Infection <em>In Vivo</em&gt. Antimicrob Agents Chemother 2019; 63(9): e01142-19.
[http://dx.doi.org/10.1128/AAC.01142-19] [PMID: 31307979]
[39]
DeWald LE, Johnson JC, Gerhardt DM, et al. In Vivo Activity of Amodiaquine against Ebola Virus Infection. Sci Rep 2019; 9(1): 20199.
[http://dx.doi.org/10.1038/s41598-019-56481-0] [PMID: 31882748]
[40]
Goyal S, Binnington B, McCarthy SDS, et al. Inhibition of in vitro Ebola infection by anti-parasitic quinoline derivatives. F1000 Res 2020; 9: 268-8.
[http://dx.doi.org/10.12688/f1000research.22352.1] [PMID: 32528661]
[41]
Boonyasuppayakorn S, Reichert ED, Manzano M, Nagarajan K, Padmanabhan R. Amodiaquine, an antimalarial drug, inhibits dengue virus type 2 replication and infectivity. Antiviral Res 2014; 106: 125-34.
[http://dx.doi.org/10.1016/j.antiviral.2014.03.014] [PMID: 24680954]
[42]
Kos J, et al. 8-Hydroxyquinoline-2-Carboxanilides as Antiviral Agents Against Avian Influenza Virus. ChemistrySelect 2019; 4(15): 4582-7.
[http://dx.doi.org/10.1002/slct.201900873]
[43]
Barbosa-Lima G, Moraes AM, Araújo ADS, et al. 2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine. Eur J Med Chem 2017; 127: 334-40.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.058] [PMID: 28068604]
[44]
McDonagh P, Sheehy PA, Fawcett A, Norris JM. Antiviral effect of mefloquine on feline calicivirus in vitro. Vet Microbiol 2015; 176(3-4): 370-7.
[http://dx.doi.org/10.1016/j.vetmic.2015.02.007] [PMID: 25746684]
[45]
Sun W, He S, Martínez-Romero C, et al. Synergistic drug combination effectively blocks Ebola virus infection. Antiviral Res 2017; 137: 165-72.
[http://dx.doi.org/10.1016/j.antiviral.2016.11.017] [PMID: 27890675]
[46]
Carta A, Briguglio I, Piras S, et al. Quinoline tricyclic derivatives. Design, synthesis and evaluation of the antiviral activity of three new classes of RNA-dependent RNA polymerase inhibitors. Bioorg Med Chem 2011; 19(23): 7070-84.
[http://dx.doi.org/10.1016/j.bmc.2011.10.009] [PMID: 22047799]
[47]
Overacker RD, Banerjee S, Neuhaus GF, et al. Biological evaluation of molecules of the azaBINOL class as antiviral agents: Inhibition of HIV-1 RNase H activity by 7-isopropoxy-8-(naphth-1-yl)quinoline. Bioorg Med Chem 2019; 27(16): 3595-604.
[http://dx.doi.org/10.1016/j.bmc.2019.06.044] [PMID: 31285097]
[48]
Shiroishi-Wakatsuki T, Maejima-Kitagawa M, Hamano A, et al. Discovery of 4-oxoquinolines, a new chemical class of anti-HIV-1 compounds. Antiviral Res 2019; 162: 101-9.
[http://dx.doi.org/10.1016/j.antiviral.2018.12.012] [PMID: 30582937]
[49]
Althaus IW, Gonzales AJ, Chou JJ, et al. The quinoline U-78036 is a potent inhibitor of HIV-1 reverse transcriptase. J Biol Chem 1993; 268(20): 14875-80.
[PMID: 7686907]
[50]
Witvrouw M, Daelemans D, Pannecouque C, et al. Broad-spectrum antiviral activity and mechanism of antiviral action of the fluoroquinolone derivative K-12. Antivir Chem Chemother 1998; 9(5): 403-11.
[http://dx.doi.org/10.1177/095632029800900504] [PMID: 9875393]
[51]
Al-Saad D, Memeo MG, Quadrelli P. #Nitrosocarbonyls 1: antiviral activity of N-(4-hydroxycyclohex-2-en-1-yl)quinoline-2- carboxamide against the influenza A virus H1N1. Scientific-WorldJournal 2014; 2014
[http://dx.doi.org/10.1155/2014/472373] [PMID: 25610906]
[52]
Kassem EM, El-Sawy ER, Abd-Alla HI, Mandour AH, Abdel-Mogeed D, El-Safty MM. Synthesis, antimicrobial, and antiviral activities of some new 5-sulphonamido-8-hydroxyquinoline derivatives. Arch Pharm Res 2012; 35(6): 955-64.
[http://dx.doi.org/10.1007/s12272-012-0602-0] [PMID: 22870804]
[53]
Musharrafieh R, Zhang J, Tuohy P, et al. Discovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68). J Med Chem 2019; 62(8): 4074-90.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00115] [PMID: 30912944]
[54]
Marois I, Cloutier A, Meunier I, Weingartl HM, Cantin AM, Richter MV. Inhibition of influenza virus replication by targeting broad host cell pathways. PLoS One 2014; 9(10)
[http://dx.doi.org/10.1371/journal.pone.0110631] [PMID: 25333287]
[55]
Baroni A, Paoletti I, Ruocco E, et al. Antiviral effects of quinine sulfate on HSV-1 HaCat cells infected: analysis of the molecular mechanisms involved. J Dermatol Sci 2007; 47(3): 253-5.
[http://dx.doi.org/10.1016/j.jdermsci.2007.05.009] [PMID: 17600687]
[56]
Malakar S, Sreelatha L, Dechtawewat T, et al. Drug repurposing of quinine as antiviral against dengue virus infection. Virus Res 2018; 255: 171-8.
[http://dx.doi.org/10.1016/j.virusres.2018.07.018] [PMID: 30055216]
[57]
Li J, Seupel R, Feineis D, et al. Dioncophyllines C2, D2, and F and Related Naphthylisoquinoline Alkaloids from the Congolese Liana Ancistrocladus ileboensis with Potent Activities against Plasmodium falciparum and against Multiple Myeloma and Leukemia Cell Lines. J Nat Prod 2017; 80(2): 443-58.
[http://dx.doi.org/10.1021/acs.jnatprod.6b00967] [PMID: 28121440]
[58]
Uzor PF. Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies . Evid Based Complement Alternat Med 2020; 2020.
[http://dx.doi.org/10.1155/2020/8749083 ] [PMID: 32104196]
[59]
Fadaeinasab M, Taha H, Fauzi PN, Ali HM, Widyawaruyanti A. Anti-malarial Activity of Isoquinoline Alkaloids from the Stem Bark of Actinodaphne macrophylla. Nat Prod Commun 2015; 10(9): 1541-2.
[http://dx.doi.org/10.1177/1934578X1501000913] [PMID: 26594753]
[60]
Nasrullah AA, Zahari A, Mohamad J, Awang K. Antiplasmodial alkaloids from the bark of Cryptocarya nigra (Lauraceae). Molecules 2013; 18(7): 8009-17.
[http://dx.doi.org/10.3390/molecules18078009] [PMID: 23884132]
[61]
Zahari A, Ablat A, Sivasothy Y, Mohamad J, Choudhary MI, Awang K. In vitro antiplasmodial and antioxidant activities of bisbenzylisoquinoline alkaloids from Alseodaphne corneri Kosterm. Asian Pac J Trop Med 2016; 9(4): 328-32.
[http://dx.doi.org/10.1016/j.apjtm.2016.03.008] [PMID: 27086149]
[62]
Bostanciklioglu M. Severe acute respiratory syndrome coronavirus 2 is penetrating to dementia research. Curr Neurovasc Res 2020.
[http://dx.doi.org/10.2174/1567202617666200522220509] [PMID: 32442082]
[63]
Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020; 17(5): 259-60.
[http://dx.doi.org/10.1038/s41569-020-0360-5] [PMID: 32139904]
[64]
Read R. Flawed methods in “COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv 2020.
[65]
Solomon VR, Haq W, Srivastava K, Puri SK, Katti SB. Synthesis and antimalarial activity of side chain modified 4-aminoquinoline derivatives. J Med Chem 2007; 50(2): 394-8.
[http://dx.doi.org/10.1021/jm061002i] [PMID: 17228883]
[66]
Kondaparla S. Synthesis and antimalarial activity of new 4-aminoquinolines active against drug resistant strains. RSC Advances 2016; 107 In press
[67]
Aguiar ACC, Murce E, Cortopassi WA, et al. Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity. Int J Parasitol Drugs Drug Resist 2018; 8(3): 459-64.
[http://dx.doi.org/10.1016/j.ijpddr.2018.10.002] [PMID: 30396013]
[68]
te Velthuis AJW, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog 2010; 6(11)e1001176
[http://dx.doi.org/10.1371/journal.ppat.1001176] [PMID: 21079686]

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