From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy

Abstract

Malarial treatment is widely and readily available today. However, there was a time in the not-so-distant past when malaria was a deadly disease with no known cause or cure. In this article, we trace the origins of an antimalarial therapy from the discovery of the nature of the malarial parasite through the development of chloroquine. We dedicate this article to Johann "Hans" Andersag, the scientist who developed chloroquine, on the 110th anniversary of his birth, 16 February 1902.

“Recycling” Classical Drugs for Malaria

“…29 Only three years later, Bayer gave birth to what was going to become the most emblematic antimalarial of the 20th century: the 4-aminoquinoline (4-AQ) resochin, or chloroquine (CQ, Figure 6), whose potency, bioavailability and safety outshined those of all antimalarials available by then. 30 Those three classical antimalarial drugs from Bayer represented the rise of the three major classes of 20th century antimalarials: 8-aminoquinolines, acridines and 4-aminoquinolines. The relevance of these three families of antimalarials is still felt at present day, since many such compounds are still used in the clinical setting, and also because medicinal chemists worldwide keep up using their scaffolds as templates toward creation of better drugs.…”

“…It was only after this event that resochin was rediscovered and renamed as chloroquine in 1945, by E. K. Marshall. 30 The CQ's superior antimalarial properties were soon recognized, and it was designated the antimalarial drug of choice due to its high efficacy, low cost, and tolerable adverse effects.…”

An atomic scale mechanism for the antimalarial action of chloroquine from density functional theory calculations

“…Chloroquine was first prepared and investigated as an antimalarial in 1934, and has saved countless lives since that time [12]. Although CQ also disrupts the growth of haemozoin crystals, the molecular basis of its action has remained obscure.…”

Chloroquine Has a Cytotoxic Effect on Acanthamoeba Encystation through Modulation of Autophagy

“…Chloroquine has been used to treat amoebic liver abscess, malaria, and inflammatory diseases (17)(18)(19)(20). The mechanism of chloroquine in amoebic liver abscess has not been well identified.…”