Expanding horizons for clinical applications of chloroquine, hydroxychloroquine, and related structural analogues

Abstract

Several experimental and clinical studies have transformed the traditional antimalarial role of chloroquine (CHQ) and related structural analogues to potent therapeutic agents for a host of nonmalarial indications. The expanding clinical applicability for these drugs includes rheumatological and cardiovascular disorders (CVD), chronic kidney disease (CKD), oncology, and a variety of nonmalarial infections. These clinical advancements are primarily related to pleiotropic pharmacological actions of these drugs, including immunomodulation, anti-inflammatory properties, and capabilities of inducing autophagy and apoptosis at a cellular level. Historically, many clinical benefits in nonmalarial indications were first recognized through serendipitous observations; however, with numerous ongoing systematic clinical studies, the clinical horizons of these drugs have a promising future.

The trinity of COVID-19: immunity, inflammation and intervention

“…91 ). Although hydroxychloroquine's effect on direct inhibition of the virus 92 and its anti-inflammatory and immunomodulatory activities are known 93 , whether these mechanisms play a role against COVID-19 remains to be determined 94 .…”

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) are aminoquinolinic compounds currently registered for the treatment and prevention of malaria and for the treatment of a number of autoimmune diseases. CQ was developed in the 1930s and extensively used during World War II to prevent and treat malaria infection [74], but its use as an antimalarial is now very limited due to the widespread resistance of Plasmodium.…”

Hydroxychloroquine: A Potential Ethical Dilemma for Rheumatologists during the COVID-19 Pandemic

“…During World War II, there were serendipitous observations of improved autoimmune skin disease and arthritis associated with CQ use 5 . Toxicity related to CQ was reduced when HCQ was developed by the addition of a β-hydroxy chain to the CQ molecule 6 .…”