326 2. MALE ATE 



Chromatography of tumor cells and ascites fluid showed no free glutamine 

 or changes in amino acid pattern. The LD50 of maleurate given intrape- 

 ritoneally to mice is 775 mg/kg, and 150 mg/kg/day is tolerated for 8 days 

 without evidence of toxicity (Siskin et al., 1959). It was found that a dose 

 of 250 mg/kg almost completely inhibits the incorporation of thymidine-H^ 

 into ascites cells. There is thus interference with DNA formation and a 

 delay in the entrance of interphase cells into mitosis. Various esters of 

 maleurate are more effective than maleurate, perhaps because of better 

 penetration, but the esters affect the formation of the cleavage spindles 

 whereas maleurate does not, so that the mechanisms of action may not 

 be exactly the same (Okada and Roberts, 1963). It was possible to ad- 

 minister doses, which produce abnormalities in the tumor cells without 

 being generally toxic or affecting survival. Maleurate and its derivatives 

 exert very interesting effects on cleavage and it is likely that further in- 

 vestigation will provide some insight into mitotic processes. 



MALErC HYDRAZIDE 



Maleic hydrazide was introduced in 1949 by the U. S. Rubber Company 

 as a new type of plant growth regulator and herbicide, following the initial 

 report by Schoene and Hoffmann (1949) that this substance produces 

 a unique depression of growth, the inhibition being marked but temporary 

 and often unaccompanied by damage to the plants. If tomato plants are 

 sprayed with 0.2% maleic hydrazide, growth stops for 2 months but the 

 plants remain normal during this time, except for some chlorosis of the 

 lower leaves. There is no terminal growth but the leaves grow to their 

 normal size. Maleic hydrazide has come to be an important commercial 

 herbicide, and much work has been done to elucidate the mechanism by 

 which it so selectively suppresses growth of plants. We shall not discuss 

 the effects on plants in detail; a complete review of this aspect of the subject 

 has been provided by Crafts (1961 a). The treatment here will be confined 

 to those properties possibly relating maleic hydrazide to maleate and reac- 

 tion with SH groups, and to what little is known of the effects on plant 

 metabolism. 



Structure, Properties, and Reactions 



Maleic hydrazide is commonly written as structure (I), but there is 

 evidence that structures (II) and (IV) may contribute significantly. 

 (1) Maleic hydrazide is a fairly strong acid (piiT^ = 5.65), which would 

 not be expected from structure (I); however, the resonance form (IV) 

 of the tautomeric structure (II) would account for the lability of a proton 

 (Feuer and Rubinstein, 1958). (2) The ultraviolet spectrum of maleic hy- 

 drazide is similar to that of 6-hydroxy-2-methyl-3(2//)-pyridazinone, in- 



