A novel and one-pot synthesis of new 1-tosyl pyrrol-2-one derivatives and analysis of carbonic anhydrase inhibitory potencies.
Here we propose a novel one-pot synthesis of new tosyl-pyrrole derivatives. By means of the new developed method, pyrrole derivatives were synthesized at room temperature in a single step, and a useful method is proposed for the synthesis of similar compounds. Moreover, inhibitions of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II by 1-tosyl-pyrrole and 1-tosyl-pyrrol-2-on derivatives were investigated. 1-Tosyl-pyrrole, 1-tosyl-1H-pyrrol-2(5H)-one, 5-hydroxy-1-tosyl-1H-pyrrol-2(5H)-one and 5-oxo-1-tosyl-2,5-dihydro-1H-pyrrol-2-yl acetate showed inhibitory action with K(i) values in the range of 14.6-42.4 microM for hCA I and 0.53-37.5 microM for hCA II, respectively. All pyrrole derivatives were competitive inhibitors with 4-nitrophenylacetate as substrate. Some new synthesized pyrrole derivatives showed very effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors targeting other CA isoforms.
Alp
Cemalettin
C
Atatürk University, Science Faculty, Department of Chemistry, Erzurum, Turkey.
Ekinci
Deniz
D
Gültekin
Mehmet Serdar
MS
Sentürk
Murat
M
Sahin
Ertan
E
Küfrevioğlu
Omer Irfan
OI
D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D002257:Carbonic Anhydrase Inhibitors; D011758:Pyrroles; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II