Hadacidin, a new inhibitor of purine biosynthesis.

The inhibition of purine biosynthesis has been observed with the use of various types of compounds. The antibiotics O-diazoacetyl-n-serine (azaserine) and 6-diazo-5-oxo-n-norleucine suppress purine formation by virtue of their antagonistic action toward glutamine in amination reactions (l-3). Several structural analogues of purine and of pteroylglutamic acid are also known to block the biosynthesis of purine nucleotides. The literature pertaining to these antimetabolites has recently been extensively reviewed (4-6). The fermentation broth of Penicillium jrequentuns (Westling) was found to show growth-inhibitory activity against human adenocarcinoma (HAD No. 1) growing in the embryonated egg.’ -1 substance possessing the same activity was subsequently isolated from the broth and found to have the structure shown in Formula 1 (7).