Chemistry and Biology of Hydroxamic Acids

The action of salicylhydroxamic acid and its halogen derivatives against tuberculosis, fungi, trypanosomae, and the biosynthesis of cholesterol are described. Their hypoglycemic and phospholipid lowering actions are also mentioned. The author suggested, in 1948, the use of salicylhydroxamic acid I (X = Y = Z = R = H)—called SH—as an antitubercular agent [26]. The suggestion was based on the hypothesis that the hydroxamic group can act as an aminating agent, either as a source of hydroxylamine [14, 25] or through the Lossen degradation, and its effect might, therefore, be similar to that of p-aminosalicylic acid (PAS), a well-known antitubercular drug. Results with SH on exper­ imental tuberculosis in animals were encouraging. Its acute toxicity was found to be extremely low; the L D 5 0 by oral administration was 3.0 g/kg, but its antitubercular activity in clinical experiments was not significant. In a search for more potent agents among the derivatives of SH, 5-bromosalicylhydroxamic acid I (X = Y = R = H , Z = Br) was prepared [27, 23]. This derivative will be referred to as BSH. Like SH, its toxicity was found to be very low [28]. Mclsaac and Williams [20] explained the low toxicity of these compounds from studies of their metabolism. They found that both SH and BSH are metabolized mainly by direct conjugation with glucuronic acid and sulphuric acid, thus producing I (X = Y = Z = H , R = C 6 H 9 O e or R = SO ; iH) and I (X = Y = H , Z = Br, R = C K H 9 0 6 or SO : !H), respectively.