Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases

J Antimicrob Chemother. 2015;70(6):1608-21. doi: 10.1093/jac/dkv018. Epub 2015 Feb 17.

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.

Keywords: SLE; hydroxychloroquine; lysosomotropic actions; quinacrine; therapies; toxicity profiles.

Publication types

  • Review

MeSH terms

  • Antimalarials / adverse effects
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / pharmacology
  • Cardiovascular Agents / therapeutic use
  • Chloroquine / adverse effects
  • Chloroquine / pharmacology
  • Chloroquine / therapeutic use*
  • Drug Repositioning / trends*
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Hydroxychloroquine / adverse effects
  • Hydroxychloroquine / pharmacology
  • Hydroxychloroquine / therapeutic use*
  • Immunologic Factors / adverse effects
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use

Substances

  • Antimalarials
  • Antineoplastic Agents
  • Cardiovascular Agents
  • Immunologic Factors
  • Hydroxychloroquine
  • Chloroquine