Quinine and congeners

Replication of DNA requires the separation of the two companion strands of the parental double-helical structure, and substances that interfere with strand separation should inhibit DNA replication. Moreover, RNA transcription from DNA requires the availability of certain base pairs, and constraint of these pairs will hinder the process. Thus, one of the modes of action of chloroquine, quinacrine, and quinine, and their congeners, is an inhibition of DNA replication primarily, but also of. RNA transcription from DNA secondarily, mediated throu inhibition of the respective DNA and RNA polymerase reactions. Whether these processes take place in vivo... 

Recently, guettardine was obtained from the bark of Guettarda heterosepala in a 0.025% yield (17). This alkaloid can be considered to be an intermediate between the corynanthe and the cinchonamine-type alkaloids that are precursors and congeners of quinine (Fig. 5.2.20). 

Quinacrine and its congeners display substantia] activity against the asexual erythrocytic forms of plasmodia that cause human malaria, but they are neither causally prophylactic nor radically curative and have no action on the gametocytes. The acridines are therefore used for suppressive therapy and they resemble the 4-aminoquinolines and quinine in this respect quinacrine is less toxic and more elfective than quinine but more toxic and less effective than chloroquine. The recommended regimen for quinacrine to terminate acute malarial attacks is 2800 mg given over seven days, with initial administration of five loading doses of 200 mg every six hours to... 

Squaramides offer yet another variant of the bis-NH proton donor with different geometry compared to thioureas and their congeners. Thus, the quinine-derived squaramide (238b) can catalyse Michael addition of -dicarbonyls to ArCH=CHN02. Here, brine has been found to provide remarkable rate acceleration and a higher level of stereoselectivity (>98% ee) over organic solvents, presumably because of the hydrophobic hydration effect. ... 

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