Novel sulphamides and sulphonamides incorporating the tetralin scaffold as carbonic anhydrase and acetylcholine esterase inhibitors.
Reactions of amino, aminomethyl tetralins and benzyl alcohol with chlorosulphonyl isocyanate (CSI) afforded sulphamoyl carbamates. The sulphamoyl carbamates were converted to sulphamides by palladium-catalysed hydrogenolysis. Sulphonamides were synthesized from the reactions of amines with MeSO2 Cl. Inhibition of human (h) carbonic anhydrase (CA) isoenzymes (hCA I, hCA II) and acetylcholine esterase (AChE) was investigated with the synthesized compounds. hCA I and hCA II were inhibited in the low micromolar or sub-micromolar range. The Ki values were in the range of 0.91-9.56 µM against hCA I and of 3.70-27.88 µM against hCA II. Sulphamides 11-13 and sulphonamides 14-16 had moderate inhibition capacity toward AChE. These findings suggest the novel sulphamides 11-13 and sulphonamides 14-16 as AChE and CA isoenzyme inhibitory agents.
Central Researching Laboratory, Agri Ibrahim Cecen University, Agri, Turkey; Faculty of Science, Department of Chemistry, Atatürk University, Erzurum, Turkey.
Akın
A
Akıncıoğlu
Meryem
M
Topal
Ilhami
I
Gülçin
Süleyman
S
Göksu
D000110:Acetylcholinesterase / Q000378:metabolism; 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* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D002800:Cholinesterase Inhibitors; D058851:GPI-Linked Proteins; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; C548244:ACHE protein, human; D000110:Acetylcholinesterase; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
Acetylcholine esterase; Aminotetralins; Carbonic anhydrase; Sulphamides; Sulphamoyl carbamates; Sulphonamides