Microwave assisted synthesis of novel acridine-acetazolamide conjugates and investigation of their inhibition effects on human carbonic anhydrase isoforms hCA I, II, IV and VII

详细信息    查看全文

• 作者：Ramazan Ulus^a ; Burak Aday^a ; Muhammet Tanç ; ^b ; Claudiu T. Supuran^b ; ^{claudiu.supuran@unifi.it" class="auth_mail" title="E-mail the corresponding author} ; Muharrem Kaya^c ; ^{muharrem.kaya@dpu.edu.tr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CA ; carbonic anhydrase ; hCA ; human carbonic anhydrase ; Quinacrine ; (RS)-N&prime ; -(6-Chloro-2-methoxy-acridin-9-yl)-N ; N-diethylpentane-1 ; 4-diamine ; Proflavine ; acridine-3 ; 6-di-amine ; Amsacrine ; N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide ; IR ; infrared ; NMR ; nuclear magnetic resonance ; HRMS ; high resolution mass spectroscopy ; SAR ; structure&ndash ; activity relationship ; DMSO ; dimethyl sulfoxide ; TLC ; thin layer chromatography ; mp ; melting point ; ESI ; electron spray ionization ; TEA
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：24
• 期：16
• 页码：3548-3555
• 全文大小：455 K

文摘

4-Amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)benzamide was condensed with cyclic-1,3-diketones (dimedone and cyclohexane-1,3-dione) and aromatic aldehydes under microwave irradiation, leading to a series of acridine–acetazolamide conjugates. The new compounds were investigated as inhibitors of carbonic anhydrases (CA, EC 4.2.1.1), and more precisely cytosolic isoforms hCA I, II, VII and membrane-bound one hCA IV. All investigated isoforms were inhibited in low micromolar and nanomolar range by the new compounds. hCA IV and VII were inhibited with K_Is in the range of 29.7–708.8 nM (hCA IV), and of 1.3–90.7 nM (hCA VII). For hCA I and II the K_Is were in the range of 6.7–335.2 nM (hCA I) and of 0.5–55.4 nM (hCA II). The structure–activity relationships (SAR) for the inhibition of these isoforms with the acridine–acetazolamide conjugates reported here were delineated.