Synthesis of novel acridine bis-sulfonamides with effective inhibitory activity against the carbonic anhydrase isoforms I, II, IX and XII. Issue 20 (15th October 2015)

• Record Type: Journal Article
• Authors: Esirden, İbrahim; Ulus, Ramazan; Aday, Burak; Tanç, Muhammet; Supuran, Claudiu T.; Kaya, Muharrem
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 20(2015)
• Page Start: 6573
• Page End: 6580
• Publication Date: 2015-10-15
• Subjects: MCR multi component reaction -- CA carbonic anhydrase -- hCA human carbonic anhydrase -- NADH nicotinamide adenine dinucleotide -- Amsacrine N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide -- Asulacrine 9-[4-(methanesulfonamido)-2-methoxyanilino]-N, 5-dimethylacridine-4-carboxamide -- Acronycine 6-methoxy-3, 3, 12-trimethylpyrano[2, 3-c]acridin-7-one -- DACA N-[2-(dimethylamino)ethyl]acridine-4-carboxamide -- Proflavine acridine-3, 6-diamine -- Ascididemin 9H-quino[4, 3, 2-de][1, 10]phenanthrolin-9-one -- CAIs carbonic anhydrase inhibitors -- IR infrared -- NMR nuclear magnetic resonance -- HRMS high resolution mass spectroscopy -- SAR structure–activity relationship -- DMSO dimethyl sulfoxide -- LC liquid chromatography -- DBSA p-dodecylbenzenesulfonic acid -- TLC tine layer chromatography -- mp melting point -- Lit literature -- ESI electron spray ionization -- TEA trimethylamine -- μM micromolar -- nM nanomolar -- KI inhibition constant; Carbonic anhydrase -- Acridine -- Sulfonamide -- Enzyme inhibition -- Isoforms CA I, II, IX and VII; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.09.022
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: By using a multi component reaction system (MCR), nitro acridine sulfonamides were obtained from cyclic-1, 3-diketones, 4-aminobenzene sulfonamide and aromatic aldehydes. Some novel acridine bis-sulfonamides6a –l were then synthesized by the reaction between sulfonyl chlorides and the novel amino-acridine sulfonamides5a and5b, obtained by reduction of nitro-acridine sulfonamide derivatives4a and4b . The newly synthesized compounds were investigated as inhibitors of 4 human carbonic anhydrase isoforms (hCA, EC 4.2.1.1). Several of the compounds showed low micromolar inhibition against the medically relevant isoforms hCA I, II, IX, and XII.