Synthesis of new cyclic thioureas and evaluation of their metal-chelating activity, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibition profiles. 2017

Parham Taslimi, and Afsun Sujayev, and Emin Garibov, and Nazar Nazarov, and Zubeyir Huyut, and Saleh H Alwasel, and İlhami Gulçin
Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey.

In the presence of trifluoracetic acid (TFAA), an efficient method for the synthesis of tetra(hexa)hydropyrimidinethione-carboxylates has been used on the basis of three-component condensation of thiourea with its different aldehydes and β-diketones. Some novel cyclic thioureas were synthesized, and their hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitors and metal-chelating properties were evaluated. Ki values of novel synthesized compounds for AChE and BChE are in the range of 51.84-135.96 and 143.96-274.55 nM, respectively. Also, HCA I and II were effectively inhibited by these novel compounds, with Ki values in the range of 404.16-745.13 nM for hCA I and of 434.20-689.57 nM for hCA II, respectively. Additionally, acetazolamide (AZA), clinically used as a CA inhibitor, with a Ki value of 883.68 ± 121.27 nM in hCA I and 1008.66 ± 144.70 nM in hCA II. Also, tacrine inhibited AChE and BChE showed Ki values of 314.63 ± 31.66 and 373.57 ± 75.07 nM, respectively.

UI MeSH Term Description Entries
D002091 Butyrylcholinesterase An aspect of cholinesterase (EC 3.1.1.8). Pseudocholinesterase,Benzoylcholinesterase,Butyrylthiocholinesterase
D002256 Carbonic Anhydrases A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 4.2.1.1. Carbonate Dehydratase,Carbonic Anhydrase,Anhydrases, Carbonic,Dehydratase, Carbonate
D002257 Carbonic Anhydrase Inhibitors A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES. Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D000110 Acetylcholinesterase An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D013890 Thiourea A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.

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