Inhibition of human prostatic tumour acid phosphatase by N,N-p-di-2-chloroethylaminophenol, N,N-p-di-2-chloroethylaminophenyl phosphate and other difunctional nitrogen mustards.

Potent inhibition of human prostatic carcinoma tissue acid phosphatase by N,N-d-di-2-chloroethylaminophenol (AMOH) and N,N-p-di-2-chloroethylaminophenyl phosphate (AMPh) is described. Certain other difunctional nitrogen mustards were also inhibitory but N,N-p-di-2hydroxyethylaminophenol, the non-alkylating fully hydrolysed product from AMOH, was not. Inactivation of the enzyme by AMPh was progressive with time, showed apparent first order reaction kinetics and was not reversed by extensive dialysis. The results suggest that the inability of the enzyme to catalyse the hydrolysis of AMPh was due to inhibition in the presence of AMPh, possibly involving an alkylating mechanism. The implications for possible chemotherapy with AMPh are discussed.