Menoctone

Quinones and naphthoquinones were explored during the World War 11 Antimalarial Dmg Program. Now that chloroquine resistance is a serious problem, compounds of this group such as menoctone (76) are being reinvestigated. 

There are no hiUy effective therapeutic agents for the treatment of thederiasis. Chlorotetracycline (20) and oxytetracycline (3) have therapeutic activity duting the iacubation period. Pamaquiae (68) was reported to have a specific effect on the erythrocyctic forms. Other dmgs with limited efficacy are imidocarb (19) on T annulata halofugiaone (45) on both T annulata and T parva and the naphthoquiaones menoctone (76), parvaquone (88), and buparvaquone (89) on T parva. Methotrexate (90) has been found to be active in vitro (Table 9). 

The importance of naphthoquinones, particularly 2-hydroxy-3-alkyl-l,4-naphthoquinones, in chemotherapy of malaria came to light when a naphthoquinone, hydrolapachol (9), was found to possess activity against P. lophurai in ducks [8]. This observation prompted Fieser and coworkers [9-13] to synthesize a series of substituted naphthoquinones, of which lapinone (10) and menoctone (11) emerged as promising antimalarials. 

Fieser and coworkers [70] have developed an elegant method to synthesize 2-hydroxy-3-(cyclohexylalkyl)-l,4-naphthoquinones. Menoctone (11) may be prepared starting form 5-phenylvaIeric acid (83) by the reaction sequence given in scheme 2. 

McHardy, N. (1978). In vitro studies on the action of menoctone and other compounds on Theileria parva and T. annulata. Ann. Trop. Med. Parasitol. 72, 501-511. 

Hudson, A.T. Lapinone, menoctone, hydroxyquinolinequinones and similar structures. In Antimalarial Drugs volume II (Eds. Peters,W., Richards,W.H.G.), Springer-Verlag, Berlin, 1984, 343... 

The binding of 8-amlnoquinollne antlmalarials to DNA conqparable to that with chloroquine has been reported.7° effect on DNA fxmction may be involved with antimalarlal activity. Co-en nne Q which is associated with the mitochondrial oxidation of DPNH and succinate and is present in the metabolism of the parasite has been shown to be inhibited by chloroquine, primaquine, quinacrine and menoctone (IV), thus suggesting diversity of action for antimalarial drags.77... 

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