title: Captopril/enalapril inhibit promiscuous esterase activity of carbonic anhydrase at micromolar concentrations: An in vitro study.
abstract: The inhibitory activity of captopril, a thiol-containing competitive inhibitor of the angiotensin-converting enzyme, ACE, against esterase activity of carbonic anhydrase, CA was investigated. This small molecule, as well as enalapril, was selected in order to represents both thiol and carboxylate, as two well-known metal binding functional groups of metalloprotein inhibitors. Since captopril, has also been observed to inhibit other metalloenzymes such as tyrosinase and metallo-beta lactamase through binding to the catalytic metal ions and regarding CA as a zinc-containing metallo-enzyme, in the current study, we set out to determine whether captopril/enalapril inhibit CA esterase activity of the purified human CA II or not? Then, we revealed the inhibitors' potencies (IC50, Kiand Kdissvalues) and also mode of inhibition. Our results also showed that enalapril is more potent CA inhibitor than captopril. Since enalapril represents no sulfhydryl moiety, thus carboxylate group may have a determinant role in inhibiting of CA esterase activity, the conclusion confirmed by molecular docking studies. Additionally, since CA inhibitory potencies of captopril/enalapril were much lower than those of classic sulfonamide drugs, the findings of the current study may explain why these drugs exhibit no effective CA inhibition at the concentrations reached in vivo and also may shed light on the way of generating new class of inhibitors that will discriminately inhibit various CA isoforms.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Esmaeili
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ashrafi-Kooshk
authors.affiliation: Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Adibi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: rkhodarahmi@mbrc.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Khodarahmi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D024402:Carbonic Anhydrase II / Q000187:drug effects*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D004950:Esterases / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002257:Carbonic Anhydrase Inhibitors; D004656:Enalapril; D002216:Captopril; D004950:Esterases; D024402:Carbonic Anhydrase II
keywords: CA; Captopril; Enalapril; Inhibition