Inhibitory effect of synthetic aminophosphonic acid derivatives on human carbonic anhydrase

Abstract

A series of phosphonic analogs of amino acids, peptides and their derivatives was synthesized in order to examine their ability to inhibit human carbonic anhydrase (HCA) isoenzymes (I and II). The aminophosphonic acids with amino protection possess much stronger inhibitory capacity ( K i = 10 −6-10 −5 M) than the free aminophosphonic acids ( K i = 10 −5-10 −3 M). The aminophosphonic acids with both N- and P-protection do not have an inhibitory effect on the esterase activity of HCA. In a comparison of the enantiomeric pairs of Cbz-Ala P(OH) 2, the d-conformer has several-fold stronger inhibitory potency. All aminoalkylphosphonates investigated possess one order of magnitude stronger inhibitory activity towards isoenzyme HCA-I than towards HCA-II. A computer-directed analysis was used to study the possible interactions in an aminoalkylphosphonate [Cbz- d-Ala P(OH) 2]-(HCA-II) complex.