Hadacidin

Hadacidin, and hadacidin analogues, have anticancer activity and activity against adenylosuccinate synthetase.

The hydroxylamino group of hydroxamic acids of fungal origin has a nitrogen with oxidation state of - 1. The hydroxylamino group is frequently donated by a hydroxylamino acid (N-hydroxyamino acid), such as 8-N-hydroxyornithine of the siderochromes. Hadacidin is the simplest known naturally occurring hydroxamic acid. This compound, isolated and characterized by Kaczka et al. (1962), seemed well suited for a study of the route of hydroxamic acid biosynthesis. The hydroxamate bond may be considered to be a peptide bond with an oxygen atom on the amide nitrogen, but there is no a priori reason to decide whether the oxygen atom is introduced before or after the formation of the amide bond. In the latter case, formylglycine would be an intermediate in hadacidin biosynthesis. N-Hydroxylation of an amide bond was reported by Cramer et al. (1960), who found that N-hydroxy-2-acetylaminofluorene was formed in the intact rat upon administration of 2-acetylaminofluorene. Nevertheless, this finding cannot be considered direct proof of N-hydroxylation of an amide bond because, as the authors point out, the acetyl group is labile in their experiments, and hydroxylation of the amino group might have occurred.