Synthesis and carbonic anhydrase inhibitory properties of sulfamides structurally related to dopamine

• Published in: Bioorganic & medicinal chemistry 2013-06, Vol.21 (11), p.2925-2931
• Main Authors: Aksu, Kadir, Nar, Meryem, Tanc, Muhammet, Vullo, Daniela, Gülçin, İlhami, Göksu, Süleyman, Tümer, Ferhan, Supuran, Claudiu T.
• Format: Article
• Language: English
• Subjects: alcohols; Amines - chemistry; anti-infective agents; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Obesity Agents - chemical synthesis; Anti-Obesity Agents - chemistry; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; antineoplastic agents; Benzyl Alcohol - chemistry; Candida glabrata; Candida glabrata - chemistry; Candida glabrata - enzymology; carbamates; carbonate dehydratase; Carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrases - chemistry; Dopamine; Dopamine - chemistry; Enzyme inhibition; Humans; Isocyanates - chemistry; isozymes; Mycobacterium tuberculosis; Mycobacterium tuberculosis - chemistry; Mycobacterium tuberculosis - enzymology; Structure-Activity Relationship; Sulfamide; Sulfamoyl carbamates; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; tert-Butyl Alcohol - chemistry
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.03.077

Carbonic anhydrase (CA) inhibitory properties of sulfamide derivatives of dopamine related compounds were investigated. These compounds showed promising CA inhibitory properties. A series of novel sulfamides incorporating the dopamine scaffold were synthesized. Reaction of amines and tert-butyl-alcohol/benzyl alcohol in the presence of chlorosulfonyl isocyanate (CSI) afforded sulfamoyl carbamates, which were converted to the title compounds by treatment with trifluoroacetic acid or by palladium-catalyzed hydrogenolysis. Inhibition of six α-carbonic anhydrases (CAs, EC 4.2.1.1), that is, CA I, CA II, CA VA, CA IX, CA XII and CA XIV, and two β-CAs from Candida glabrata (CgCA) and Mycobacterium tuberculosis (Rv3588) with these sulfamides was investigated. All CA isozymes were inhibited in the low micromolar to nanomolar range by the dopamine sulfamide analogues. Kis were in the range of 0.061–1.822μM for CA I, 1.47–2.94nM for CA II, 2.25–3.34μM for CA VA, 0.041–0.37μM for CA IX, 0.021–1.52μM for CA XII, 0.007–0.219μM for CA XIV, 0.35–5.31μM for CgCA and 0.465–4.29μM for Rv3588. The synthesized sulfamides may lead to inhibitors targeting medicinally relevant CA isoforms with potential applications as antiepileptic, antiobesity antitumor agents or anti-infective.