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Review Article

New Trends in Biological Activities and Clinical Studies of Quinolinic Analogues: A Review

Author(s): Sandra Elizabeth Barbosa da Silva, José Arion da Silva Moura , Tiago Rafael de Sousa Nunes , Ivan da Rocha Pitta and Marina Galdino da Rocha Pitta*

Volume 23, Issue 5, 2022

Published on: 28 March, 2022

Page: [441 - 457] Pages: 17

DOI: 10.2174/1389450122666210415100151

Price: $65

Abstract

The quinolinic ring, present in several molecules, possesses a great diversity of biological activities. Therefore, this ring is in the structural composition of several candidates of drugs in preclinical and clinical studies; thus, it is necessary to compile these results to facilitate the design of new drugs. For this reason, some of the activities of compounds are selected to examine in this review, such as antimalarial, antimicrobial, anticancer, anti-inflammatory, antidiabetic, anti-rheumatic, and antiviral activities. All publications of scientific articles chosen are dated between 2000 and 2020. In addition to presenting the structures of some natural and synthetic compounds with their activities, we have listed the clinical studies of phases III and IV on antimalarial drugs containing the quinoline nucleus and phase III clinical studies on hydroxychloroquine and chloroquine to assess their possible role in COVID-19. Finally, we have reviewed some of the mechanisms of action, as well as the side effects of some of the quinolinic derivatives.

Keywords: Clinical trials, quinolinic ring, antimalarials, COVID-19, pharmacology, chloroquine.

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Graphical Abstract

[1]
Joshi SD, Jangade NM, Dixit SR, Joshi AS, Kulkarni VH. Quinoline: a promising and versatile scaffold for future. Indo Amer J Pharm Res 2016; 6(04): 5033-44.
[2]
Simões CMO, Schenkel EP, Gosmann G, Mello JCP, Mentz LA, Petrovick PR. Pharmacognosy: from plant to drug Porto Alegre 2003; 765-80.
[3]
Manzali de Sá I. Resistance to chloroquine and the search for antimalarials between the 1960s and 1980s. Hist Cienc Saude Manguinhos 2011; 18(2): 407-30.
[4]
World Health Organization; Available from:. https://www. mmv.org/sites/default/files/uploads/docs/publications/World%20Malaria%20Report_0.pdf (Accessed January 2021).
[5]
Çapcı A, Lorion MM, Wang H, et al. Artemisinin-(Iso)quinoline hybrids by C-H activation and click chemistry: combating multidrug-resistant malaria. Angew Chem Int Ed Engl 2019; 58(37): 13066-79.
[http://dx.doi.org/10.1002/anie.201907224] [PMID: 31290221]
[6]
Freedman A. Chloroquine and rheumatoid arthritis; a short-term controlled trial. Ann Rheum Dis 1956; 15(3): 251-7.
[http://dx.doi.org/10.1136/ard.15.3.251] [PMID: 13363258]
[7]
Othman DIA, Selim KB, El-Sayed MAA, et al. Design, synthesis and anticancer evaluation of new substituted thiophene-quinoline derivatives. Bioorg Med Chem 2019; 27(19) ,115026.
[http://dx.doi.org/10.1016/j.bmc.2019.07.042] [PMID: 31416740]
[8]
Musharrafieh R, Kitamura N, Hu Y, Wang J. Development of broad-spectrum enterovirus antivirals based on quinoline scaffold. Bioorg Chem 2020; 101 ;103981.
[http://dx.doi.org/10.1016/j.bioorg.2020.103981] [PMID: 32559580]
[9]
Gao P, Wang L, Zhao L, et al. Anti-inflammatory quinoline alkaloids from the root bark of Dictamnus dasycarpus. Phytochemis 2020; 172 ;112260.
[http://dx.doi.org/10.1016/j.phytochem.2020.112260] [PMID: 31982646]
[10]
Singh SK, Singh S. A brief history of quinoline as antimalarial agents. Int J Pharm Sci Rev Res 2014; 25(1): 295-302.
[11]
Cunico W, Carvalho SA, Gomes CRB, Marques CH. Anti-malarial drugs-history and perspectives. Revista Brasileira de Famácia 2008; 89(1): 49-55.
[12]
Han X, Lamshöft M, Grobe N, et al. The biosynthesis of papaverine proceeds via (S)-reticuline. Phytochemistry 2010; 71(11-12): 1305-12.
[http://dx.doi.org/10.1016/j.phytochem.2010.04.022] [PMID: 20494383]
[13]
Anderberg PI, Harding MM, Lay PA. The effect of metal ions on the electrochemistry of the antitumor antibiotic streptonigrin. J Inorg Biochem 2004; 98(5): 720-6.
[http://dx.doi.org/10.1016/j.jinorgbio.2003.10.011] [PMID: 15134917]
[14]
Olajide OA, Ajayi AM, Wright CW. Anti-inflammatory properties of cryptolepine. Phytother Res 2009; 23(10): 1421-5.
[http://dx.doi.org/10.1002/ptr.2794] [PMID: 19288476]
[15]
World Health Organization; Available from:. https://apps.who. int/iris/bitstream/handle/10665/275867/9789241565653-eng.pdf? ua=1 (Accessed July 2019).
[16]
Soares RR, da Silva JM, Carlos BC, et al. New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Bioorg Med Chem Lett 2015; 25(11): 2308-13.
[http://dx.doi.org/10.1016/j.bmcl.2015.04.014] [PMID: 25920564]
[17]
Kumar S, Bawa S, Gupta H. Biological activities of quinoline derivatives. Mini Rev Med Chem 2009; 9(14): 1648-54.
[http://dx.doi.org/10.2174/138955709791012247] [PMID: 20088783]
[18]
Ghorab MM, Alsaid MS. Anti-breast cancer activity of some novel quinoline derivatives. Acta Pharm 2015; 65(3): 271-83.
[http://dx.doi.org/10.1515/acph-2015-0030] [PMID: 26431105]
[19]
Bispo MLF, Alcantara CC, Moraes MO, et al. A new and potent class of quinoline derivatives against câncer. Monatsh Chem 2015; 146: 2041-52.
[http://dx.doi.org/10.1007/s00706-015-1570-0]
[20]
Srikanth L, Raghunandan N, Siriniva P, Amarender RG. Synthesis and evaluation of newer quinoline derivatives of Thiazolidinediones for their antidiabetic activity. Int J Pharm Bio Sci 2010; 1(4)
[21]
Edmont D, Rocher R, Plisson C. chenault J. Synthesis and evaluation of quinoline carboxyguanidines as antidiabetic agents. Bioorg Med Chem Lett 2000; 10(16): 1831-4.
[22]
Rogachev AD, Kuranov SO, Salakhutdinov NF. Chemical approach to the design of affective antidiabectic agents. Russian Chem Rev 2016; 85(12): 1313-37.
[23]
Souza MVN, Almeida MV, Silva AD, Couri MRC. Ciprofloxacina, uma importante fluorquinolona no combate ao antraz. Rev Bras Farm 2004; 85(1): 13-8.
[24]
Shivaraj Y, Naveen MH, Vijayakumar GR, Kumar DBA. Design, synthesis and antibacterial activity studies of novel quinoline carboxamide derivatives. J Korean Chem Soc 2013; 2: 241-5.
[http://dx.doi.org/10.5012/jkcs.2013.57.2.241]
[25]
Sumana T, Iyengar P, Sanjeevarayappa C. Synthesis, characterization and antimicrobial activity of pharmaceutically important 1,2-dihydroquinoline derivatives. J Appl Chem 2015; 4(3): 818-27.
[26]
Zarghi A, Ghodsi R, Azizi E, Daraie B, Hedayati M, Dadrass OG. Synthesis and biological evaluation of new 4-carboxyl quinoline derivatives as cyclooxygenase-2 inhibitors. Bioorg Med Chem 2009; 17(14): 5312-7.
[http://dx.doi.org/10.1016/j.bmc.2009.05.084] [PMID: 19560931]
[27]
Mazzoni O, Esposito G, Diurno MV, et al. Synthesis and pharmacological evaluation of some 4-oxoquinoline-2-carboxylic acid derivatives as anti-inflammatory and analgesic agents. Arch Pharm Chem Life Sci 2010; 10: 561-9.
[http://dx.doi.org/10.1002/ardp.201000016]
[28]
Wen X, Wang S, Liu D, Gong G, Quan Z. Synthesis and evaluation of the anti-inflammatory activity of quinoline derivatives. Med Chem Res 2015; 24: 2591-603.
[http://dx.doi.org/10.1007/s00044-015-1323-y]
[29]
de Meneses Santos R, Barros PR, Bortoluzzi JH, et al. Synthesis and evaluation of the anti-nociceptive and anti-inflammatory activity of 4-aminoquinoline derivatives. Bioorg Med Chem 2015; 23(15): 4390-6.
[http://dx.doi.org/10.1016/j.bmc.2015.06.029] [PMID: 26116178]
[30]
Mukherjee S, Pal M. Quinolines: a new hope against inflammation. Drug Discov Today 2013; 18(7-8): 389-98.
[http://dx.doi.org/10.1016/j.drudis.2012.11.003] [PMID: 23159484]
[31]
Buckley GM, Cooper N, Dyke HJ, et al. 8-Methoxyquinoline-5-carboxamides as PDE4 inhibitors: a potential treatment for asthma. Bioorg Med Chem Lett 2002; 12(12): 1613-5.
[http://dx.doi.org/10.1016/S0960-894X(02)00223-8] [PMID: 12039574]
[32]
Billah M, Buckley GM, Cooper N, et al. 8-Methoxyquinolines as PDE4 inhibitors. Bioorg Med Chem Lett 2002; 12(12): 1617-9.
[http://dx.doi.org/10.1016/S0960-894X(02)00224-X] [PMID: 12039575]
[33]
Feldmann M. Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol 2002; 2(5): 364-71.
[http://dx.doi.org/10.1038/nri802] [PMID: 12033742]
[34]
Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum 1993; 23(2)(Suppl. 1): 82-91.
[http://dx.doi.org/10.1016/S0049-0172(10)80012-5] [PMID: 8278823]
[35]
Silva JC, Mariz HA, Rocha LF Jr, et al. Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients. Clinics (São Paulo) 2013; 68(6): 766-71.
[http://dx.doi.org/10.6061/clinics/2013(06)07] [PMID: 23778483]
[36]
Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res 2018; 6: 15.
[http://dx.doi.org/10.1038/s41413-018-0016-9]
[37]
Li C, Zhu X, Ji X, et al. Chloroquine, a FDA-approved drug, prevents zika virus infection and its associated congenital microcephaly in mice. Ebiomedicine 2017; 24: 189-94.
[PMID: 29736302]
[38]
Bedoya LM, Abad MJ, Calonge E, et al. Quinoline-based compounds as modulators of HIV transcription through NF-κB and Sp1 inhibition. Antiviral Res 2010; 87(3): 338-44.
[http://dx.doi.org/10.1016/j.antiviral.2010.06.006]
[39]
Perin N, Alic J, Liekens S, et al. Different positions of amide side chains on the benzimidazo[1,2-a]quinoline skeleton strongly influence biological activity. N J Chem 2018; 42(9): 7096-104.
[40]
Shang X, Morris-Natschke SL, Liu Y, et al. Biologically active quinoline and quinazoline alkaloids part I. Med Res Rev 2017; 38(3): 775-828.
[41]
Evaluating the efficacy of chloroquine for the treatment of Plasmodium vivax infections in Central Vietnam. National Institute of Malariology, Parasitology and Entomology, Vietnam 2016. Available from:. https://clinicaltrials.gov/ct2/show/NCT02610686
[42]
Pharmacokinetic study of multi-dose chloroquine 2014. Available from:. https://clinicaltrials.gov/ct2/show/NCT01814423?term=Chl oroquine&phase=23&rank=4 (Accessed February 2019).
[43]
Extended-dose C. hloroquine (ECQ) for resistant falciparum malaria among Afghan Refugees in Pakistan (ECQNWFP). 2009. Available from:. https://clinicaltrials.gov/ct2/show/NCT01019408? term=Chloroquine&phase=23&rank=13 (Accessed February 2019).
[44]
Chloroquine for treatment of glioblastoma multiforme. 2009. Available from:. https://clinicaltrials.gov/ct2/show/NCT00224978? term=Chloroquine&phase=23&rank=18 (Accessed February 2019).
[45]
Prevention of P. vivax malaria during pregnancy in bolivia. 2013. Available from: . https://clinicaltrials.gov/ct2/show/NCT00290420? term=Chloroquine&phase=23&rank=21 (Accessed February 2019).
[46]
Cura Chik. A trial of the efficacy and safety of chloroquine as therapeutic treatment of chikungunya disease 2015.Available from:. https://clinicaltrials.gov/ct2/show/NCT00391313?term=Chloroquine&phase=23&rank=2 (Accessed February 2019).
[47]
Estimating the risk of Plasmodium vivax relapses in Afghanistan (VRA). 2019. Available from:. https://clinicaltrials.gov/ct2/show/ NCT01178021?term=Chloroquine&phase=23&rank=27 (Accessed February 2019).
[48]
Pharmacoepidemiological evaluation of autophagy inhibition in treatment of HCV Patients resistant to standard therapy. Pilot Study 2015. Available from:. https://clinicaltrials.gov/ct2/show/ NCT02058173?term=Chloroquine&phase=23&rank=39 (Accessed February 2019).
[49]
Efficacy study of hydroxychloroquine to treat high-risk coronary artery disease. CHANGAN 2017. Available from:. https://clinical trials.gov/ct2/show/NCT02874287?term=hydroxychloroquine& phase=23&rank=1
[50]
Hydroxychloroquine for the prevention of cardiovascular events in myocardial infarction Patients - a Safety Pilot Trial (OXI). 2018. Available from:. https://clinicaltrials.gov/ct2/show/NCT02648464? term=hydroxychloroquine&phase=23&rank=2 (Accessed February 2019).
[51]
Hydroxychloroquine treatment of dry eyes in patients with primary sjögren's syndrome. 2013. Available from:. https://clinicaltrials. gov/ct2/show/NCT01601028?term=hydroxychloroquine&phase=2 3&rank= (Accessed February 2019).
[52]
Hydroxychloroquine for prevention of recurrent miscarriage. 2019. Available from:. https://clinicaltrials.gov/ct2/show/NCT 03165136?term=hydroxychloroquine&phase=23&rank=4 (Accessed February 2019).
[53]
Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome (PAPIRUS). 2018. Available from:. https://clinicaltrials.gov/ct2/show/NCT03540810? term=hydroxychloroquine&phase=23&rank=5(Accessed February 2019).
[54]
[54] Hydroxychloroquine for the first thrombosis prevention in antiphospholipid antibody positive patients. 2017. Available from:. https://clinicaltrials.gov/ct2/show/NCT01784523?term=hydroxychloroquine&phase=23&rank=6(Accessed February 2019).
[55]
Hydroxychloroquine to improve insulin sensitivity in rheumatoid arthritis (RA PLUS). 2014. Available from:. https://clinicaltrials. gov/ct2/show/NCT01132118?term=hydroxychloroquine&phase=23&rank=7(Accessed February 2019).
[56]
Reducing risk of type 2 diabetes: hydroxychloroquine use in prediabetes. 2016. Available from:. https://clinicaltrials.gov/ct2/show/NCT01326533?term=hydroxychloroquine&phase=23&rank=8 (Accessed February 2019).
[57]
Hydroxychloroquine versus placebo in primary sjögren's syndrome (JOQUER). 2012. Available from:. https://clinicaltrials. gov/ct2/show/NCT00632866?term=hydroxychloroquine&phase=23&rank=9 (Accessed February 2019).
[58]
Hydroxychloroquine and cognitive function after surgery. 2018. Available from:. https://clinicaltrials.gov/ct2/show/NCT03025087? term=hydroxychloroquine&phase=23&rank=1 (Accessed February 2019).
[59]
Hydroxychloroquine sulfate for reduction of proteinuria in patients with IgA Nephropathy: a Self- Controlled Study. 2013. Available from:. https://clinicaltrials.gov/ct2/show/NCT02351752?term=hydroxychloroquine&phase=23&rank=13 (Accessed February 2019).
[60]
Effect of hydroxychloroquine on atrial fibrillation recurrence. 2018. Available from:. https://clinicaltrials.gov/ct2/show/NCT03592823?term=hydroxychloroquine&phase=23&rank=15 (Access ed February 2019).
[61]
Multicenter study assessing the efficacy & safety of hydroxychloroquine sulfate in patients with systemic lupus erythematosus or cutaneous lupus erythematosus with active lupus erythematosus specific skin lesion 2014. Available from:. https://clinicaltrials. gov/ct2/show/NCT01551069?term=hydroxychloroquine&phase=23&rank=16 (Accessed February 2019).
[62]
Hydroxychloroquine (HCQ) for Recurrent Pregnancy Loss; 2018.Available from:. https://clinicaltrials.gov/ct2/show/NCT03305263? term=hydroxychloroquine&phase=23&rank=17 (Accessed February 2019).
[63]
Hydroxychloroquine in giant cell arteritis. 2015. Available from:. https://clinicaltrials.gov/ct2/show/NCT00430807?term=hydroxychloroquine&phase=23&rank=18 (Accessed February 2019).
[64]
The reduction of systemic lupus erythematosus flares: Study PLUS. 2011. Available from:. https://clinicaltrials.gov/ct2/show/NCT00413361?term=hydroxychloroquine&phase=23&rank=19 (Accessed February 2019).
[65]
Plaquenil for alopecia areata, alopecia totalis. 2009. Available from:. https://clinicaltrials.gov/ct2/show/NCT00176982?term=hydroxychloroquine&phase=23&rank=21 (Accessed February 2019).
[66]
Pharmacological treatment in osteoarthritis (FABIO). 2015. Available from:. https://clinicaltrials.gov/ct2/show/NCT01148043? term=hydroxychloroquine&phase=23&rank=23 (Accessed February 2019).
[67]
Efficacy of intrarectal versus intravenous quinine for the treatment of childhood cerebral malaria. 2005. Available from:. https://clinicaltrials.gov/ct2/show/NCT00124267?term=quinine&phase=23&rank=6 (Accessed February 2019).
[68]
A bioequivalence study comparing camoquin® suspension (Pfizer) To Flavoquine® Tablets (Sanofi Aventis) In Healthy Subjects. 2010. Available from:. https://clinicaltrials.gov/ct2/show/NCT00859807?term=amodiaquine&phase=23&rank=4 (Accessed February 2019).
[69]
Single Low-dose primaquine Efficacy and Safety. 2017. Available from:. https://clinicaltrials.gov/ct2/show/NCT02090036?titles=Single+Low-dose+primaquine+Efficacy+and+Safety&rank=2 (Access ed February 2019).
[70]
Investigation of short course, high dose primaquine treatment for liver stages of plasmodium vivax infection. 2015. Available from:. https://clinicaltrials.gov/ct2/show/NCT02364583?titles=Investigation+of+Short+Course%2C+High+Dose+primaquine&rank=1 (Accessed February 2019).
[71]
A trial on supervised primaquine use in Ethiopia. 2016. Available from:. https://clinicaltrials.gov/ct2/show/NCT02793388?titles=A+Trial+on+Supervised+Primaquine+Use+in+Ethiopia&rank=1 (Accessed February 2019).
[72]
Evaluation of the gametocytocidal efficacy and safety of primaquine in uncomplicated Falciparum Malaria in Uganda. 2011. Available from:. https://clinicaltrials.gov/ct2/show/NCT01365598? titles=Evaluation+of+the+Gametocytocidal+Efficacy+and+Safety+of+Primaquine+in+Uncomplicated+Falciparum+Malaria+in+Ug anda&rank=1 (Accessed February 2019).
[73]
Keyaerts E, Vijgen L, Maes P, Neyts J, Ranst MV. In vitro inhibition of severe acute respiratoy syndrome coronavirus by chloroquine. In: Biochemcial and Biophysical Research Communications. 2004; pp. 264-8.
[74]
Vincent MJ, Bergeron E, Erickson BR, et al. Chloroquine is a potente inhibitor of SARS coronavirus infection and spread. Virol J 2005; 1-10.
[75]
Marella A, Tanwar OP, Saha R, et al. Quinoline: A versatile heterocyclic. Saudi Pharm J 2013; 21(1): 1-12.
[http://dx.doi.org/10.1016/j.jsps.2012.03.002] [PMID: 23960814]
[76]
Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: randomized controlled, open-label, phase 3 clinical trial. Avaialble from:. https://clinicaltrials.gov/ct2/show/ NCT04414241?term=Hydroxychloroquine&cond=SARS-COV-2 &phase=2&draw=2&rank=1 (Accessed July 2020).
[77]
A study of hydroxychloroquine as post exposure prophylaxis for SARS-CoV-2(HOPETrial). Available from:. https://clinicaltrials. gov/ct2/show/NCT04330144?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=4 (Accessed July 2020).
[78]
A randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of oral hydroxychloroquine for the treatment of SARS-CoV-2 positive patients for the prevention of severe COVID-19 Disease. Available from:. https://clinicaltrials.gov/ct2/show/NCT04329611?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=7 (Accessed July 2020).
[79]
Hydroxychloroquine efficacy and safety in preventing SARSCoV- 2 Infection and COVID-19 disease severity during pregnancy. Available from:. https://clinicaltrials.gov/ct2/show/NCT04410562?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=8 (Accessed July 2020).
[80]
Immune monitoring of prophylactic effect of hydroxychloroquine in healthcare providers highly exposed to SARS-Cov-2. Available from:. altrials.gov/ct2/show/NCT04346329?term=Hydroxychloroquine&cond=SARS-COV2&phase=2&draw (Accessed July 2020).
[81]
Efficacy and safety of hydroxychloroquine for covid-19 postexposure prophylaxis of healthcare workers in the philippine general hospital and up Manila National Institutes of health: a randomized, double-blind, placebo-controlled trial. Randomized A. Available from:. https://clinicaltrials.gov/ct2/show/NCT04364815? term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw =2&rank=16 (Accessed July 2020).
[82]
Hydroxychloroquine for the treatment of mild COVID-19 Disease. Available from:. https://clinicaltrials.gov/ct2/show/NCT04340544? term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw =2&rank=18 (Accessed July 2020).
[83]
Efficacy of hydroxychloroquine (hcq) as post exposure prophylaxis (pep) for prevention of covid-19 in asymptomatic individual at risk for sars-cov-2 infection-A Open Level Control Clinical Trial. Available from:. https://clinicaltrials.gov/ct2/show/NCT04408456? term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw =2&rank=19 (Accessed July 2020).
[84]
A randomized, controlled clinical trial of the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 in hospitalized patients. Available from:. https://clinicaltrials.gov/ct2/show/NCT04345692?term=Hydroxychloroquine&cond=SARS-COV-2 &phase=2&draw=2&rank=23 (Accessed July 2020).
[85]
Randomized controlled trial of hydroxychloroquine versus placebo for the treatment of adult patients with acute coronavirus disease 2019 - COVID-19. 2019. Available from:. https://clinicaltrials. gov/ct2/show/NCT04342221?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=26 (Accessed July 2020).
[86]
Multicentre A. Double-blinded randomized controlled trial. preexposure prophylaxis with hydroxychloroquine for high-risk healthcare workers during the covid-19 pandemic: a multicentre, double-blinded randomized controlled trial. Available from:. https://clinicaltrials.gov/ct2/show/NCT04331834?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=27 (Accessed July 2020).
[87]
Hydroxychloroquine treatment for severe covid-19 respiratory disease: randomised clinical trial (HYDRA Trial). Available from:. https://clinicaltrials.gov/ct2show/NCT04315896?term=Hydroxychloroquine&cond=SARS-COV-2&phase==2&rank=28 (Accessed July 2020).
[88]
Safety and efficacy of post-exposure prophylaxis with hydroxychloroquine (HCQ) for the Prevention of COVID-19 in highrisk older individuals in long-term and specialized care: a doubleblind randomized control trial. Available from:. https://clinicaltrials.gov/ct2/show/NCT04397328?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=31 (Accessed July 2020).
[89]
Will hydroxychloroquine impede or prevent COVID-19: WHIP COVID-19 Study. Available from:. https://clinicaltrials.gov/ct2/show/NCT04341441?term=Hydroxychloroquine&cond=SARSCOV-2&phase=2&draw=2&rank=34 (Accessed July 2020).
[90]
Efficacy and safety of hydroxychloroquine for treatment of COVID-19. Available from:. https://clinicaltrials.gov/ct2/show/NCT04261517?term=Hydroxychloroquine&cond=SARS-COV-2 &phase=2&draw=2&rank=37 (Accessed July 2020).
[91]
Low-dose hydroxychloroquine for primary prophylaxis against SARS-CoV-2 in Health-care workers - a randomized, doubleblind. Available from:. https://clinicaltrials.gov/ct2/show/NCT04336748?term=Hydroxychloroquine&cond=SARS-COV-2& phase=2&draw=2&rank=38 (Accessed July 2020).
[92]
Chemoprophylaxis with hydroxychloroquine in healthcare personnel in contact with COVID-19 patients: a randomized controlled trial (PHYDRA Trial). Available from:. https://clinicaltrials. gov/ct2/show/NCT04318015?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=40 (Accessed July 2020).
[93]
Post exposure prophylaxis (pep) in healthcare workers exposed to COVID-19 Patients: A double-blind randomized clinical Trial. https://clinicaltrials.gov/ct2/show/NCT04437693?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=41 (Accessed July 2020).
[94]
Randomized controlled trial of hydroxychloroquine versus placebo in early ambulatory diagnosis and treatment of elderly COVID19 patients. Available from:. https://clinicaltrials.gov/ct2/show/NCT04351516?term=Hydroxychloroquine&cond=SARS-COV-2& phase=2&draw=2&rank=44 (Accessed July 2020).
[95]
Chemoprophylaxis for covid-19 infectious disease (the PROLIFIC Trial). Available from: https://clinicaltrials.gov/ct2/show/NCT04352933?term=Hydroxychloroquine&cond=SARS-COV-2& phase=2&draw=2&rank=44 (Accessed July 2020).
[96]
Randomized A. Placebo-controlled multi-site trial in Toronto, Canada. Protecting Frontline health care workers from COVID-19 with hydroxychloroquine pre-exposure prophylaxis: a randomized, placebo-controlled multi-site trial in Toronto, Canada. Available from:. https://clinicaltrials.gov/ct2/show/NCT04374942?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=47 (Accessed July 2020).
[97]
Hydroxychloroquine as primary prophylaxis for COVID-19 in Healthcare Workers (HCQPreP). Available from:. clinicaltrials.gov/ct2/show/NCT04363450?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=50 (Accessed July 2020).
[98]
Assessment of the efficacy and safety of hydroxychloroquine (hcq) administered as a prophylaxis for health professionals exposed to COVID19 and working in medical intensive care units, in Tunisia. Multicentric randomized comparative study. Available from:. https://clinicaltrials.gov/ct2/show/NCT04349228?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=51 (Accessed July 2020).
[99]
Efficacy of early hydroxychloroquine in outpatients to reduce secondary hospitalisation and household transmission of COVID- 19 in Switzerland: A Double-blind, Randomised, Placebocontrolled Trial. Available from:. https://clinicaltrials.gov/ct2/show/NCT04385264?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=52 (Accessed July 2020).
[100]
A randomized phase 2/3 trial of hydroxychloroquine In Covid-19 Kinetics. Available from:. https://clinicaltrials.gov/ct2/show/NCT04353271?term=Hydroxychloroquine&cond=SARS-COV-2& phase=2&draw=2&rank=53 (Accessed July 2020).
[101]
Efficacy of hydroxychloroquine for post-exposure prophylaxis (pep) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults exposed to coronavirus disease (COVID-19): a Blinded, Randomized Study. Available from:. https://clinicaltrials.gov/ct2/show/NCT04328961?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=54 (Accessed July 2020).
[102]
Prophylaxis for paTiEnts at Risk of COVID-19 infecTion (PROTECT): a basket trial of prophylactic interventions amongst at-risk patients. Available from:. https://clinicaltrials.gov/ct2/show/NCT04389359?term=Hydroxychloroquine&cond=SARS-COV-2&pha se=2&draw=2&rank=55 (Accessed July 2020).
[103]
Hydroxychloroquine post exposure prophylaxis (pep) for household contacts of covid-19 patients: a nyc community-based randomized clinical trial. Available from:. https://clinicaltrials. gov/ct2/show/NCT04318444?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=59 (Accessed July 2020).
[104]
Outcomes related to COVID-19 treated with hydroxychloroquine among in-patients with symptomatic disease. Available from:. https://clinicaltrials.gov/ct2/show/NCT04332991?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=61 (Accessed July 2020).
[105]
Randomized A. Protecting health care workers from COVID-19 With hydroxychloroquine pre-exposure prophylaxis: a randomized, placebo-controlled trialAvailable from: https://clinicaltrials. gov/ct2/show/NCT04352946?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=62 (Accessed July 2020).
[106]
Healthcare worker exposure response and outcomes of hydroxychloroquine trial (HERO-HCQ Trial). Available from:. https://clinicaltrials.gov/ct2/show/NCT04334148?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=68 (Accessed July 2020).
[107]
Safety and efficacy of hydroxychloroquine for at risk population (sharp) against COVID-19. a cluster randomized controlled trial (SHARP COVID-19 RCT) available from:. https://clinicaltrials. gov/ct2/show/NCT04342156?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=71 (Accessed July 2020).
[108]
Prevention of COVID19 infection by the administration of hydroxychloroquine to institutionalized older people and nursing home staff. A cluster randomized controlled stepped-wedge trial (PREVICHARM Study) Available from:. https://clinicaltrials. gov/ct2/show/NCT04400019?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=72 (Accessed July 2020).
[109]
Hydroxychloroquine to prevent COVID-19 disease amongst healthcare workers (PROVIDE): a parallel randomized controlled trial. Available from: https:. https://clinicaltrials.gov/ct2/show/NCT04371523?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=74 (Accessed July 2020).
[110]
Hydroxychloroquine versus placebo in patients presenting covid- 19 infection and at risk of secondary complication: a prospective, multicentre, randomised, Double-blind Study. Available from:. https://clinicaltrials.gov/ct2/show/NCT04325893?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=76 (Accessed July 2020).
[111]
Preemptive therapy for SARS-Coronavirus-2 (COVID-19 PEP Canada). Available from:. https://clinicaltrials.gov/ct2/show/NCT04421664?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=78 (Accessed July 2020).
[112]
Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial. Available from:. https://clinicaltrials. gov/ct2/show/NCT04328467?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=2&rank=95 (Accessed July 2020).
[113]
Post-exposure prophylaxis or preemptive therapy for SARSCoronavirus- 2: A pragmatic randomized clinical trial. Available from:. https://clinicaltrials.gov/ct2/show/NCT04308668?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=3&rank=103 (Accessed July 2020).
[114]
Randomized, double-blind, controlled trial of hydroxychloroquine vs. placebo as post-exposure prophylaxis against COVID-19 infection. Available from: https:. https://clinicaltrials.gov/ct2/show/NCT04372017?term=Hydroxychloroquine&cond=SARS-COV-2&phase=2&draw=4&rank=3 (Accessed July 2020).
[115]
An International, multi-site, bayesian platform adaptive, randomised, double-blind, placebo-controlled trial assessing the effectiveness of varied doses of oral chloroquine in preventing or reducing the severity of COVID-19 disease in healthcare workers. Available from:. https://clinicaltrials.gov/ct2/show/NCT04333732?cond=chloroquine+SARS-COV-2&phase=2&draw=2&rank=3 (Accessed July 2020).
[116]
Chloroquine for mild symptomatic and asymptomatic COVID-19 in A Two Staged, multicenter, open label and randomized trial. Available from:. https://clinicaltrials.gov/ct2/show/NCT04333628? cond=chloroquine+SARS-COV-2&phase=2&draw=2&rank=5 (Accessed July 2020).
[117]
Clinical study evaluating the efficacy of chloroquine in COVID-19 Treatment. Available from:. https://clinicaltrials.gov/ct2/show/NCT04353336?cond=chloroquine+SARS-COV-2&phase=2&draw=2&rank=6 (Accessed July 2020).
[118]
Rang HP. dale MM, Ritter JM, Moore PK. Pharmacology. Br J Clin Pharmacol 2004; 57(1): 112.
[http://dx.doi.org/10.1111/j.1365-2125.2004.01916.x]
[119]
Lewis RJ, Tsai FTF, Wigley DB. Molecular mechanisms of drug inhibition of DNA gyrase. BioEssays 1996; 18(8): 661-71.
[http://dx.doi.org/10.1002/bies.950180810] [PMID: 8760340]
[120]
Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry 2014; 53(10): 1565-74.
[http://dx.doi.org/10.1021/bi5000564] [PMID: 24576155]
[121]
Homewood CA, Warhurst DC, Peters W, Baggaley VC. Lysosomes, pH and the anti-malarial action of chloroquine. Nature 1972; 235(5332): 50-2.
[http://dx.doi.org/10.1038/235050a0] [PMID: 4550396]
[122]
Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology 2015; 23(5): 231-69.
[http://dx.doi.org/10.1007/s10787-015-0239-y] [PMID: 26246395]
[123]
Rynes RI. Antimalarial drugs in the treatment of rheumatological diseases. Br J Rheumatol 1997; 36(7): 799-805.
[http://dx.doi.org/10.1093/rheumatology/36.7.799] [PMID: 9255117]
[124]
Tillotson GS. Quinolones: structure-activity relationships and future predictions. J Med Microbiol 1996; 44(5): 320-4.
[http://dx.doi.org/10.1099/00222615-44-5-320] [PMID: 8636945]
[125]
Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 2012; 42(2): 145-53.
[http://dx.doi.org/10.1007/s12016-010-8243-x] [PMID: 21221847]
[126]
Kim JW, Kim YY, Lee H, Park SH, Kim SK, Choe JY. Risk of retinal toxicity in longterm users of hydroxychloroquine. J Rheumatol 2017; 44(11): 1674-9.
[http://dx.doi.org/10.3899/jrheum.170158] [PMID: 28864645]

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