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A series of eighteen substituted pyrazoles, bis- and tris-azolyl-methanes or ethanes was investigated for their interaction with the zinc enzyme carbonic anhydrase (CA). Several types of activities were detected, generally as CA activators, but Ca inhibitory properties were also discovered for the very sterically-demanding derivatives of these series. Kinetic determinations by a stopped-flow technique for carbon dioxide hydration reaction allowed the determination of Michaelis-Menten constants, which are identical in the absence or in the presence of these modulators, proving a noncompetitive mechanism of activation-inhibition. MNDO calculations were used with moderate success to explain the biological results.

Carbonic Anhydrase Activators. XV. A Kinetic Study of the Interaction of Bovine Isozyme II with Pyrazoles, Bis- and Tris-azolyl-methanes.