title: Synthesis of N-alkyl (aril)-tetra pyrimidine thiones and investigation of their human carbonic anhydrase I and II inhibitory effects.
abstract: Tetrahydropyrimidine thiones, which are cyclic thiocarbamides derivatives, were synthesised from thiourea, β-diketones and substituted benzaldehydes. A tautomeric form of these derivatives incorporates the thiol functionality, which is known to interact with metal ions from metalloenzymes active sites, such as the carbonic anhydrases (CAs, EC 4.2.1.1) among others. This is a superfamily of widespread enzymes, which catalyses a crucial biochemical reaction, the reversible hydration of carbon dioxide to bicarbonate and protons (H(+)). The newly synthesised N-alkyl (aril)-tetrahydropyrimidine thiones were tested for inhibition of the cytosolic human isoforms I and II (hCA I and II). Both isoforms were effectively inhibited by the newly synthesised thiones. Ki values were in the range of 218.5 ± 23.9-261.0 ± 41.5 pM for hCA I, and of 181.8 ± 41.9-273.6 ± 41.4 pM for hCA II, respectively. This under-investigated class of derivatives may bring interesting insights in the field of non-sulphonamide CA inhibitors.
authors.affiliation: a Laboratory of Theoretical Bases of Synthesis and Action Mechanism of Additives , Institute of Chemistry of Additives, Azerbaijan National Academy of Sciences , Baku , Azerbaijan .
authors.forename: Afsun
authors.initials: A
authors.lastname: Sujayev
authors.affiliation: b Department of Chemistry , Faculty of Sciences, Ataturk University , Erzurum , Turkey .
authors.forename: Leyla
authors.initials: L
authors.lastname: Polat Kose
authors.affiliation: a Laboratory of Theoretical Bases of Synthesis and Action Mechanism of Additives , Institute of Chemistry of Additives, Azerbaijan National Academy of Sciences , Baku , Azerbaijan .
authors.forename: Emin
authors.initials: E
authors.lastname: Garibov
authors.affiliation: b Department of Chemistry , Faculty of Sciences, Ataturk University , Erzurum , Turkey .|c Department of Zoology , College of Science, King Saud University , Riyadh , Saudi Arabia .
authors.forename: İlhami
authors.initials: İ
authors.lastname: Gülçin
authors.affiliation: a Laboratory of Theoretical Bases of Synthesis and Action Mechanism of Additives , Institute of Chemistry of Additives, Azerbaijan National Academy of Sciences , Baku , Azerbaijan .
authors.forename: Vagif
authors.initials: V
authors.lastname: Farzaliev
authors.affiliation: c Department of Zoology , College of Science, King Saud University , Riyadh , Saudi Arabia .
authors.forename: Saleh H
authors.initials: SH
authors.lastname: Alwasel
authors.affiliation: d Dipartimento Di Chimica Ugo Schiff, Università Degli Studi Di Firenze , Sesto Fiorentino (Firenze) , Italy , and.|e Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Università Degli Studi Di Firenze , Sesto Fiorentino (Florence) , Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D013871:Thiones / Q000737:chemistry*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D011743:Pyrimidines; D013871:Thiones
keywords: Carbonic anhydrase; enzyme inhibition; pyrimidine; synthesis