Chloroquine vs Quinine: Understanding the Relationship and Historical Context

In the quest for effective antimalarial treatments, the relationship between chloroquine and quinine has been a significant point of discussion. This article explores their historical context, their structural similarities, and how they have evolved in the treatment of malaria.

Historical Background of Quinine

Before the synthesis of chloroquine and other new antimalarials, quinine was widely used to treat malaria. Quinine is a natural alkaloid obtained from the cinchona plant. This plant belongs to the genus Cinchona and has several species, including:

Among these, Cinchona ledgeriana is reported to possess the highest amount of quinine, but Cinchona calisaya is widely used as a source of quinine. These plants also contain other alkaloids such as quinidine, cinchonine, and cinchonidine, which are all quinoline alkaloids and isomers of each other.

Structural Similarities and Divergence

Chloroquine and hydroxychloroquine belong to the class of 4-amino quinolines, while quinine and mefloquine are quinoline methanols.

Observing the structure of quinidine and quinine, one can notice that they are not structurally different. They are stereo isomers of each other, differing only in their three-dimensional structure. This is a crucial distinction, as it highlights the subtle variations that can arise in chemical compounds and their biological effects.

Discovery and Synthesis of Chloroquine

The discovery and synthesis of chloroquine were the result of scientific efforts to explore the structure and properties of quinidine and quinine. These alkaloids served as lead molecules in the development of more potent and effective antimalarials, which are now widely used.

Side Effects and Safety Concerns

Quinine, despite its efficacy, is associated with serious side effects. These include QT prolongation, hemolysis due to G6 PD deficiency, and hypoglycemia. These side effects made the search for more effective and safer antimalarials a priority. Eventually, chloroquine and other modern antimalarials were synthesized.

Chloroquine not only retained the antimalarial activities of quinine but also eliminated all its side effects. Today, we have antimalarials that are more effective and have relatively fewer side effects, making natural alkaloids like quinine obsolete in the treatment of malaria.

Modern Antimalarials and Their Applications

The discovery of artemisinin marked a significant breakthrough in antimalarial therapy. Today, these drugs are widely employed to treat severe cases of malaria because they are shorter acting and are commonly combined with longer-acting antimalarial drugs to increase their effectiveness. The ACT (Artemisinin-based Combination Therapy) is the most superior antimalarial therapy available today.

However, in certain circumstances, natural antimalarials like quinine are still used. Quinine is the drug of choice in severe falciparum malaria, as the safety of artemisinin during pregnancy is not yet proven.

In conclusion, while chloroquine and quinine share a historic connection in the treatment of malaria, the evolution of modern antimalarials has shifted the focus to newer, safer, and more effective treatments.