Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors

• Published in: Journal of enzyme inhibition and medicinal chemistry 2019-12, Vol.34 (1), p.1457-1464
• Main Authors: Al-Sanea, Mohammad M, Elkamhawy, Ahmed, Paik, Sora, Bua, Silvia, Ha Lee, So, Abdelgawad, Mohamed A, Roh, Eun Joo, Eldehna, Wagdy M, Supuran, Claudiu T
• Format: Article
• Language: English
• Subjects: Benzenesulfonamides; Carbon-13 Magnetic Resonance Spectroscopy; Carbonic Anhydrase I - antagonists & inhibitors; Carbonic Anhydrase II - antagonists & inhibitors; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Humans; Proton Magnetic Resonance Spectroscopy; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology
• ISSN: 1475-6374
• DOI: 10.1080/14756366.2019.1652282

Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines reported here in variable degrees: hCA I was inhibited with s in the range of 0.966-9.091 μM, whereas hCA II in the range of 0.083-3.594 μM. The primary 7-chloro-6-flouro substituted sulphfonamide derivative ( = 0.083 μM) proved to be the most active quinoline in inhibiting hCA II, whereas, its secondary sulfonamide analog failed to inhibit the hCA II up to 10 μM, confirming the crucial role of the primary sulphfonamide group, as a zinc-binding group for CA inhibitory activity.