MALEAMATE, MALEIMIDE, AND MALEURATE 325 



late groups, and would possibly facilitate penetration into cells. Maleic 

 diamide inhibits soybean seedling growth, minimal effects being observed 

 around 0.1 mM, whereas maleamate (maleic monoamide) is only weakly 



CONH, 



inhibitory; both, however, are more effective than maleate (Parups et al., 

 1962). It is not known if these substances react readily with SH groups, 

 but it is likely since maleimide reacts very rapidly with thiols (Friedmann 

 et al., 1949). Maleimide is, however, only a moderately effective antimitotic 

 agent when examined in fibroblast cultures, inhibiting around 22% at 

 0.005-0.009 mM and producing some delay in metaphase. iV-Ethylmalei- 

 mide is much more active (see page 364). The impression is that these 

 substances may act differently than maleate, since the phase distribution 

 is not altered in the same way and the cytological changes are not identical. 

 The antimitotic activity of maleate, maleimide, iV-ethylmaleimide, and 

 maleic hydrazide prompted Okada and Roberts (1958) to study maleurate 

 (A^-carbamoylmaleamate or monomaleylurea), which combines some of 

 the structural features of the maleate group and glutamine, a substance 

 of interest in tumor metabolism. Onion root tips exposed to 5.7 milf mal- 

 eurate for 48 hr become flaccid and do not resume growth when placed 

 in fresh water. There is a marked metaphase inhibition (see accompanying 

 tabulation), which is most severe at 10 hr when 61% of the mitotic cells 



Controls Maleurate 



are in metaphase. No abnormal mitoses were observed and it was con- 

 cluded that the effects do not resemble those of any of the known antimi- 

 totic agents. The life-span of mice following inoculation with Ehrlich as- 

 cites carcinoma cells is 10-12 days; if the mice are injected with 100-300 

 mg/kg maleurate, the life-span is not altered at the lower doses and is 

 shortened somewhat at the higher, suggesting insufficient specificity 

 against the tumor cells. However, shortly after injection of maleurate there 

 is blebbing, metaphase clumping, chromosomal stickiness, and numerous 

 micronuclei, cleavage being temporarily blocked but increasing later. 



