Chloroquine and Hydroxychloroquine: The History Revisited

Abstract

The medicinal properties of the bark of the Cinchona tree have been known for centuries. It was known to cure fever and malaria. The active alkaloid was first isolated by the French chemists Pelletier and Coventou in 1820. The organized use of a large amount of quinine to prevent and treat malaria was largely done by the colonial military units in the tropics, especially in Africa and Southeast Asia. Scientists soon learned to synthesize quinine-like compounds which included chloroquine and hydroxychloroquine. Quinine (C18H26CIN3) was first synthesized successfully in 1934. In 1946, hydroxychloroquine (C18H26CIN3O) was developed as its less toxic alternative. Quinine derivatives, CQ and HCQ, are weak bases chemically. They are accumulated in acidic food vacuoles of intraerythrocytic trophozoites. Its antimalarial action is due to the induction of selective toxicity to lysosomes in parasites, thereby preventing hemoglobin degradation. For a long time the role of CQ as an anti-inflammatory agent has been investigated. It is used as a disease-modifying agent against rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It has antitumor activities also and has been studied in glioblastoma, colon, and pancreatic cancers. In the recent outbreak of the corona pandemic, there is a resurgence of interest in its use as an antiviral agent. Its mechanism of action is not fully understood; it may involve multiple pathways to act as an antiviral agent. The research activities to explore its efficacy and new applications in various diseases have never ceased. Despite its long history the drug and its derivatives have attracted scientists world-wide.