Synthesis of novel benzenesulfamide derivatives with inhibitory activity against human cytosolic carbonic anhydrase I and II and Vibrio cholerae α- and β-class enzymes

Journal of Enzyme Inhibition and Medicinal Chemistry

Alessandro Mugelli¹  Elisabetta Cerbai¹  Clemente Capasso²  Silvia Bua³  Sonia Del Prete³  Claudiu T. Supuran³  Emanuela Berrino³  Fabrizio Carta³  Vijayaparthasarathi Vijayakumar⁴  Yasinalli Tamboli⁴  Vallabhaneni S. Murthy⁴ 

[1] Department of Neurosciences, Psychology, Drug's Research and Child's Health (NEUROFARBA), University of Florence, Firenze, Italy;Section of Pharmacology and Toxicology, Firenze, Ital;Istituto di Bioscienze e Biorisorse, CNR, Napoli, Italy;NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino (Florence), Italy;School of Advanced Sciences, Center for Organic and Medicinal Chemistry, VIT University, Vellore, India;

关键词: Carbonic anhydrase inhibitors (CAIs);    sulfamides;    structure–activity relationship (SAR);    Vibrio cholerae;   

DOI  :  10.1080/14756366.2018.1467901

来源: publisher

【 摘 要 】

The synthesis of a new series of sulfamides incorporating ortho-, meta, and para-benzenesulfamide moieties is reported, which were investigated for the inhibition of two human (h) isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA I and II, and two Vibrio cholerae enzymes, belonging to the α- and β-CA classes (VchCAα, VchCAβ). The compounds were prepared by using the “tail approach”, aiming to overcome the scarcity of selective inhibition profiles associated to CA inhibitors belonging to the zinc binders. The built structure–activity relationship showed that the incorporation of benzhydryl piperazine tails on a phenyl sulfamide scaffold determines rather good efficacies against hCA I and VchCAα, with several compounds showing KIs < 100 nM. The activity was lower against hCA II and VchCAβ, probably due to the fact that the incorporated tails are quite bulky. The obtained evidences allow us to continue the investigations of different tails/zinc binding groups, with the purpose to increase the effectiveness/selectivity of such inhibitors against bacterial CAs from pathogens, affording thus potential new anti-infectives.

【 授权许可】

CC BY