Chloroquine Analogues in Drug Discovery: New Directions of Uses, Mechanisms of Actions and Toxic Manifestations from Malaria to Multifarious Diseases

Overview

Journal J Antimicrob Chemother

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2015 Feb 20

PMID 25693996

Citations 206

Authors

Md Abdul Alim Al-Bari

Affiliations

Soon will be listed here.

Abstract

Antimalarial drugs (e.g. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for many dermatological, immunological, rheumatological and severe infectious diseases, for which they are used mostly today. Chloroquine and hydroxychloroquine, two of the most fascinating drugs developed in the last 50 years, are increasingly recognized for their effectiveness in myriad non-malarial diseases. In advanced research, chloroquine and hydroxychloroquine have been shown to have various immunomodulatory and immunosuppressive effects, and currently have established roles in the management of rheumatic diseases, lupus erythematosus (different forms) and skin diseases, and in the treatment of different forms of cancer. Recently, chloroquine analogues have also been found to have metabolic, cardiovascular, antithrombotic and antineoplastic effects. This review is concerned with the lysosomotropic, anti-inflammatory and immunomodulatory mechanisms of chloroquine, hydroxychloroquine, quinacrine and related analogues, and the current evidence for both their beneficial effects and potential adverse manifestations in various diseases.

Citing Articles

Role of the NuRD complex and altered proteostasis in cancer cell quiescence.

Jiang Q, Jiang Q, Ertel M, Arrigo A, Sannino S, Goeckeler-Fried J bioRxiv. 2025; .

PMID: 39990343 PMC: 11844430. DOI: 10.1101/2025.02.10.637435.

Lipid Metabolism: An Emerging Player in Sjögren's Syndrome.

Chang K, Luo P, Guo Z, Yang L, Pu J, Han F Clin Rev Allergy Immunol. 2025; 68(1):15.

PMID: 39934534 PMC: 11813826. DOI: 10.1007/s12016-025-09023-8.

Liposomal Formulation of Hydroxychloroquine Can Inhibit Autophagy In Vivo.

Dragowska W, Singh J, Wehbe M, Anantha M, Edwards K, Gorski S Pharmaceutics. 2025; 17(1).

PMID: 39861690 PMC: 11768354. DOI: 10.3390/pharmaceutics17010042.

Functional utility of gold complexes with phosphorus donor ligands in biological systems.

Arojojoye A, Awuah S Coord Chem Rev. 2024; 522.

PMID: 39552640 PMC: 11563041. DOI: 10.1016/j.ccr.2024.216208.

Recent Advancement in Drug Development for Treating Malaria using Herbal Medicine and Nanotechnological Approach.

Bhargava S, Deshmukh R, Dewangan H Curr Pharm Des. 2024; 31(3):203-218.

PMID: 39279710 DOI: 10.2174/0113816128321468240828103439.

References

Chaturvedi S, McCrae K . Recent advances in the antiphospholipid antibody syndrome. Curr Opin Hematol. 2014; 21(5):371-9. DOI: 10.1097/MOH.0000000000000067. View

Katsanos K, Voulgari P, Tsianos E . Inflammatory bowel disease and lupus: a systematic review of the literature. J Crohns Colitis. 2012; 6(7):735-42. DOI: 10.1016/j.crohns.2012.03.005. View

Chauhan A, Khandkar M . Endocytosis of human immunodeficiency virus 1 (HIV-1) in astrocytes: a fiery path to its destination. Microb Pathog. 2014; 78:1-6. PMC: 4596405. DOI: 10.1016/j.micpath.2014.11.003. View

Yokogawa N, Kato Y, Sugii S, Inada S . Response to hydroxychloroquine in Japanese patients with systemic lupus erythematosus using the cutaneous lupus erythematosus disease area and severity index (CLASI). Mod Rheumatol. 2011; 22(2):249-55. DOI: 10.1007/s10165-011-0503-y. View

Mushtaque M, Shahjahan . Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: a review. Eur J Med Chem. 2014; 90:280-95. DOI: 10.1016/j.ejmech.2014.11.022. View

Melles R, Marmor M . Pericentral retinopathy and racial differences in hydroxychloroquine toxicity. Ophthalmology. 2014; 122(1):110-6. DOI: 10.1016/j.ophtha.2014.07.018. View

Bortoli R, Santiago M . Chloroquine ototoxicity. Clin Rheumatol. 2007; 26(11):1809-10. DOI: 10.1007/s10067-007-0662-6. View

Joshi P, Dhaneshwar S . An update on disease modifying antirheumatic drugs. Inflamm Allergy Drug Targets. 2014; 13(4):249-61. DOI: 10.2174/187152811304140915152102. View

Wallace D, Gudsoorkar V, Weisman M, Venuturupalli S . New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat Rev Rheumatol. 2012; 8(9):522-33. DOI: 10.1038/nrrheum.2012.106. View

10.

Costedoat-Chalumeau N, Dunogue B, Morel N, Le Guern V, Guettrot-Imbert G . Hydroxychloroquine: a multifaceted treatment in lupus. Presse Med. 2014; 43(6 Pt 2):e167-80. DOI: 10.1016/j.lpm.2014.03.007. View

11.

Mok C, Mak A, Ma K . Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosus. Lupus. 2005; 14(2):106-12. DOI: 10.1191/0961203305lu2039oa. View

12.

Chopra A, Saluja M, Venugopalan A . Effectiveness of chloroquine and inflammatory cytokine response in patients with early persistent musculoskeletal pain and arthritis following chikungunya virus infection. Arthritis Rheumatol. 2014; 66(2):319-26. DOI: 10.1002/art.38221. View

13.

Wahie S, Meggitt S . Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus. Br J Dermatol. 2013; 169(3):653-9. DOI: 10.1111/bjd.12378. View

14.

Palazzi C, DAmico E, DAngelo S, Gilio M, Leccese P, Olivieri I . An update on the management of hepatitis C virus-related arthritis. Expert Opin Pharmacother. 2014; 15(14):2039-45. DOI: 10.1517/14656566.2014.946404. View

15.

Kurahara D, Morie M, Yamane M, Lam S, Matthews W, Yee K . Pulmonary hemosiderosis in children with bronchopulmonary dysplasia. Case Rep Pediatr. 2014; 2014:876195. PMC: 4182842. DOI: 10.1155/2014/876195. View

16.

Yogasundaram H, Putko B, Tien J, Paterson D, Cujec B, Ringrose J . Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment. Can J Cardiol. 2014; 30(12):1706-15. DOI: 10.1016/j.cjca.2014.08.016. View

17.

Stelton C, Connors D, Walia S, Walia H . Hydrochloroquine retinopathy: characteristic presentation with review of screening. Clin Rheumatol. 2013; 32(6):895-8. DOI: 10.1007/s10067-013-2226-2. View

18.

OFarrill J, Gordon N . Autophagy in osteosarcoma. Adv Exp Med Biol. 2014; 804:147-60. DOI: 10.1007/978-3-319-04843-7_8. View

19.

van Vollenhoven R . Treatment of rheumatoid arthritis: state of the art 2009. Nat Rev Rheumatol. 2009; 5(10):531-41. DOI: 10.1038/nrrheum.2009.182. View

20.

Mar N, Kosowicz R, Hook K . Recurrent thrombosis prevention with intravenous immunoglobulin and hydroxychloroquine during pregnancy in a patient with history of catastrophic antiphospholipid syndrome and pregnancy loss. J Thromb Thrombolysis. 2014; 38(2):196-200. DOI: 10.1007/s11239-014-1061-x. View