In vitro inhibition of purified human carbonic anhydrase I and II by novel fluorene derivatives

Abstract

In this study, 9-benzylidene-9H-fluorene-substituted urea (5a-p) and thiourea derivatives (5q-v) were synthesized and their inhibitory effects on the activity of human carbonic anhydrase (hCA) I and II were evaluated. hCA I and II were purified from human erythrocytes using a Sepharose 4B-L-tyrosinesulphanilamide affinity column. All the synthesized compounds inhibited the activity of the hCA I and II isoenzymes. Among the synthesized compounds, 5f was found to be the most active (IC 50 = 21.4 μM) for inhibition of hCA I and 5s was the most active (IC 50 = 25.3 μM) for inhibition of hCA II. IN VITRO ИНХИБИЦИЈА НА ПРЕЧИСТЕНА ЧОВЕЧКА КАРБОНСКА АНХИДРАЗА I И II СО НОВИ ФЛУОРЕНСКИ ДЕРИВАТИВо оваа студија беа синтетизирани деривати на уреа (5a-p) и тиоуреа (5q-v) добиени со супституција на 9-безилиден-9H-флуорен и беше проценет нивниот инхибиторен ефект врз човечка карбонска анхидраза (hCA) I и II. HCA I и II беа пречистени од човечки еритроцити со употреба на афинитетната колона Sepharose 4B-L-тирозин-сулфаниламид. Сите синтетизирани соединенија ја инхибираа активноста на изоензимите на hCA I и II. Од синтетизираните соединенија, 5f се покажа најактивно (IC 50 = 21,4 μM) за инхибиција на hCA I, додека 5s беше најактивно (IC 50 = 25,3 μM) за инхибиција на hCA II.Клучни зборови: 9-безилиден-9H-флуорен; уреа; тиоуреа; карбонска анхидраза; инхибиција

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

“…There are many classes of compounds for CA inhibitors in the literature: (i) sulfonamides and their isosteres (such as sulfamates, sulfamides and similar derivatives) and metal complexing anions. , and (iv) the coumarins and thiocoumarins 37 , which have an inhibition mechanism not dependent of Zn(II), and bind (in hydrolyzed form) in the same active site region as the activators, occluding the entrance to the active site while the other three CAI groups bind to Zinc(II) ion or Zinc coordinated water molecule/hydroxide ion and the recently reported class of effective CAIs, (v) urea/ thiourea compounds 38,39 , (vi) b-lactames 40 . Sulfonamides have important inhibitory effect on the CA enzyme due to their ability to gain ionic structure easily and these compounds are very important in medicinal chemistry and they constitute an important class of drugs used extensively as pharmaceutical and agricultural agents 41 .…”