Tracing the Roots of Chloroquine

All accidents aren’t best avoided! Here’s an account of an accidental birth of a trump card drug of our times - Chloroquine. This drug became a promising candidate against the SARS coronavirus during the time of SARS epidemic. It had the potential to stall the replication of the virus in the body and also reduce the patient’s immune responses and thus check aggressive inflammatory action which is self-damaging to a patient’s body. Time and again with another potent variety of the coronavirus raising serious threat to life on earth, let’s time travel to the Andean jungles of South America from where the story of this accidental birth unfolds. 

The tree that shook the world… but stopped many from shivering!!

CINCHONA…what a hearty apt name for a saviour tree!! Originally known as ‘quina-quina’, it’s a high altitude tree native to the Andes region of South America. It is also called ‘The Fever Tree’. (Obviously the tree doesn’t need any introduction, but just in case… Cinchona is the tree from which Quinine, the antimalarial drug is obtained). There are two legends related to the discovery of this tree. The popular one is that in the 1600s the tree bark was used to treat fever of the Spanish Countess, ‘Chinchon’ while she was in Peru. She later introduced the bark powder which came to be known as ‘Jesuit’s bark’, ‘Cardinal’s bark’ or ‘Sacred bark’ to Europe. Finally in 1742, the botanist Carl Linnaeus named the tree ‘Cinchona’ in her honor, accidentally omitting the ‘h’. Another one states that an Indian lost in an Andean jungle with high fever, drank bitter water from a pool surrounded by Quina-Quina trees. However his fever abated and news spread among the natives about the tree’s medicinal properties.

The possession of native cinchona seeds or saplings with maximum potency was the most powerful weapon for colonial empires vying to conquer the world in the 18th and 19th centuries. Malarial infection being rampant, cinchona bark was in high demand among these empires to safeguard the health of their armies. But many independent South American republics like Peru jealously guarded the Cinchona cultivations making it difficult to obtain it. Blessings came in the form of an Englishman living in Peru, Charles Ledger, who supplied native cinchona samples to the British government. But it was the Dutch who finally succeeded in establishing good quality commercial cinchona cultivations in their colony in Java which became a turning point in World War 1 for the Allies. But the tables turned for the Allies in World War 2, when Japan conquered Java putting an end to the supply of the antimalarial drug.

During the British rule, Cinchona was brought to India too and its commercial production thrived well in the salubrious climate of the Nilgiris and in Darjeeling. However, due to overproduction the market crashed and the cultivation soon lost its sheen.

From Cinchona bark to quinine extract

It all started with the extraction of quinine (meaning ‘from the bark’) from cinchona bark in 1820 by two French scientists Pierre Pelletier and Joseph Caventou. As the old adage goes, it was the necessity for an alternative to prevent wastage of the precious Cinchona resources that led to the discovery of the active alkaloid in it called quinine. Even though there were many other alkaloids in cinchona, quinine emerged to be the most studied one, just because there was an increased supply of the Javan variety of cinchona which had higher amounts of quinine in it. It was as though the stars were conspiring for quinine to become the antimalarial drug of choice!! 

At last Chloroquine … and the German gaffe!!

With almost 80% of the quinine production met by Java, the Dutch colony, the opposite side of German troops suffered heavy casualties due to malarial infections in World War 1. The German avowal to find synthetic substitutes of quinine, taken up by ‘Bayer dye works’ German company resulted in discovery of many compounds, viz Plasmochin in 1926 and a more acceptable ‘Atabrine’ in 1932. However Atabrine was reported to cause pigmentation of skin and psychotic disorders.

Finally they came up with Resochin and Sontochin in 1934. However Resochin too was found to be over toxic and the quest for derivatives came to a standstill. Much to Germany’s dismay, this very Resochin which was termed highly toxic came out with minor adjustments by the American researchers in the form of a new potent formulation, Chloroquine during World War 2 !!

The setback

But don’t you think that’s the end of the chloroquine saga. The remarkable discovery of chloroquine however ended in a disappointment when Plasmodium attained resistance against it very shortly. Once again the traditional clinical wisdom helped overcome this hurdle. Artemisinin (extracted from Sweet wormwood or Artemisia annua widely used in Chinese medicine) combined therapies became the new beacon of hope in this juncture.

Cinchona… Quinine… and Ayurvedic wisdom

Indian traditional medicine knowledge also had in place an effective herbal armamentarium ready for usage as antiviral and antibacterial agents. Studies conducted in Malaria prevalent areas of North-east India throws light into this matter. Our own Neem tree or Indian Margosa is a classic example of a widely used antiviral agent. Some others that came up in the study include, Andrographis Paniculata, Coptis teeta, Alstonia scholaris, Acorus calamus… the list can go on.

However, after Cinchona became a widely cultivated variety in India, it also found its way to the Ayurvedic pharmacopoeia as it piqued the interest of Ayurvedic scholars. Accordingly, Cinchona is called ‘Kunayan’ or ‘Kunaina’. Out of the five fundamental pharmacological principles of Ayurveda that decide a drug’s efficacy, Cinchona has been assigned bitter taste (Rasa), hot potency (Veerya), Pungent (Vipaka) and dry and light properties (Guna) which makes it altogether a Kapha and Pitta dosha pacifying herb.

Looking back and taking a lesson or two out of history can bring fresh hope and new revelations especially in times of adversities.Let this tale of human perseverance and nature’s blessing light the path to success against the imminent threat we all face today.

About author

Dr. Jyotsna Nair

Consultant Physician, Greens Ayurveda Hospital, Azhiyur, Kozhikode.,

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