title: Synthesis and carbonic anhydrase inhibitory properties of sulfamides structurally related to dopamine.
abstract: 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. K(i)s were in the range of 0.061-1.822 μM for CA I, 1.47-2.94 nM for CA II, 2.25-3.34 μM for CA VA, 0.041-0.37 μM for CA IX, 0.021-1.52 μM for CA XII, 0.007-0.219 μM for CA XIV, 0.35-5.31 μM for CgCA and 0.465-4.29 μM 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.
authors.affiliation: Faculty of Science, Department of Chemistry, Atatürk University, 25240 Erzurum, Turkey.
authors.forename: Kadir
authors.initials: K
authors.lastname: Aksu
authors.forename: Meryem
authors.initials: M
authors.lastname: Nar
authors.forename: Muhammet
authors.initials: M
authors.lastname: Tanc
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Ilhami
authors.initials: I
authors.lastname: Gülçin
authors.forename: Süleyman
authors.initials: S
authors.lastname: Göksu
authors.forename: Ferhan
authors.initials: F
authors.lastname: Tümer
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000588:Amines / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry; D019905:Benzyl Alcohol / Q000737:chemistry; D041221:Candida glabrata / Q000737:chemistry / Q000201:enzymology; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000737:chemistry*; D004298:Dopamine / Q000737:chemistry*; D006801:Humans; D017953:Isocyanates / Q000737:chemistry; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry; D020002:tert-Butyl Alcohol / Q000737:chemistry
chemical_list: D000588:Amines; D000890:Anti-Infective Agents; D019440:Anti-Obesity Agents; D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D017953:Isocyanates; D013449:Sulfonamides; C487390:chlorosulfonyl isocyanate; D002256:Carbonic Anhydrases; D019905:Benzyl Alcohol; D020002:tert-Butyl Alcohol; D004298:Dopamine