Carbonic anhydrase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozymes I and II with some 1,3,4-oxadiazole-thiols.
A series of chiral 1,3,4-oxadiazole-5-thiols incorporating 2-substituted-benzenesulfonamide moieties has been prepared from amino acids, via the ester and carbohydrazide intermediate, followed by cyclization with carbon disulfide. Some of these compounds have been investigated for the inhibition of three physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human cytosolic hCA I and II, and the human, transmembrane, tumor-associated isozyme hCA IX. All these compounds showed weak (millimolar) affinity for the three isozymes, except two carbohydrazides and two heterocyclic thiols which selectively inhibited the tumor-associated isozyme with inhibition constants around 10 microM. Such compounds constitute interesting lead molecules for the possible design of CA IX-selective inhibitors.
Zareef
Muhammad
M
Department of Chemistry, Quaid-IAzam University, Islamabad 45320, Pakistan. mkzareef@yahoo.com
Innocenti
Alessio
A
Iqbal
Rashid
R
Zaidi
Javid H
JH
Arfan
Muhammad
M
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000970:Antineoplastic Agents / Q000737:chemistry*; D024401:Carbonic Anhydrase I / Q000737:chemistry*; D024402:Carbonic Anhydrase II / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D020033:Protein Isoforms; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013438:Sulfhydryl Compounds; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II