Currently reading Mark Sloan's 'The Ultimate Guide to Methylene Blue' Methylene blue was the precursor to (hydroxy)chloroquine. Interesting. https://www.researchgate.net/publication/221697452_From_methylene_blue_to_chloroquine_A_brief_review_of_the_development_of_an_antimalarial_therapy >From methylene to chloroquine a brief of the development of antimalarial therapy. > Paul Ehrlich (Fig. 1), a highly renowned German physician and scientist, developed a new and effective stain for blood in 1880 which he termed the neutralen Farbkörper or "neutral stain." This stain incorporated methylene blue and acid fuchsin and allowed differentiation between the different types of white blood cells. Among his remarkable accomplishments was his discovery that certain dyes could be used as drugs which would kill a specific organism while leaving other tissues unharmed. In 1891, Ehrlich discovered that methylene blue fell into this category of "magic bullet" drugs, in this case targeting the malarial organism (Fig. 2). Until this point in time, the primary treatment for malaria was quinine (Fig. 3a), a natural substance derived from the cinchona tree of South America and thus limited in supply. Ehrlich's introduction of methylene blue (Fig. 3b), a synthetic compound, allowed large-scale production of antimalarial therapy, unlimited by the supply or location of natural resources. > That same year, Gutmann and Ehrlich successfully treated two patients a domestic servant and a sailor with methylene blue (Guttmann and Ehrlich 1891). Ehrlich's student, Röhl, continued antimalarial trials with methylene blue at Bayer in Eberfield. However, methylene blue was found to be insufficiently effective to supplant quinine as an antimalarial drug. Röhl began testing the company's antimalarial compounds in birds (Figs. 4 and 5) and devised a new compound in which one methyl group was replaced by an aminoalkyl group. Scientists at Bayer began synthesizing a large number of compounds, the most successful of which was termed quinacrine (subsequently marketed as mecaprine and atabrine), which they synthesized in 1931. > Johann "Hans" Andersag (Fig. 6) was born February 16, 1902, in Lana (Meran) to Johann Andersag and Cresienz Andersag (née Tribus) ... In July, 1934, Andersag modified atabrine by replacing its acridine ring with a quinoline ring. The resulting compound, which would later be termed chloroquine (Fig. 3c), was found to have high antimalarial activity, and unlike methylene blue or atabrine, did not discolor skin and eyes.