Development of novel organometallic sulfonamides with N-ethyl or N-methyl benzenesulfonamide units as potential human carbonic anhydrase I, II, IX and XII isoforms' inhibitors: Synthesis, biological evaluation and docking studies.

Autor: Gallardo M; Departamento Química Analítica e Inorgánica, Facultad de Ciencias Químicas, Universidad de Concepción, Edmundo Larenas 129, Concepción, Chile., Arancibia R; Departamento Química Analítica e Inorgánica, Facultad de Ciencias Químicas, Universidad de Concepción, Edmundo Larenas 129, Concepción, Chile. Electronic address: rarancibia@udec.cl., Supuran CT; Neurofarba Department, University of Florence, 50019 Sesto Fiorentino, FL, Italy., Nocentini A; Neurofarba Department, University of Florence, 50019 Sesto Fiorentino, FL, Italy., Villaman D; Departamento Química Analítica e Inorgánica, Facultad de Ciencias Químicas, Universidad de Concepción, Edmundo Larenas 129, Concepción, Chile., Toro PM; Instituto de Ciencias Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, Talca, Chile. 5 Poniente 1670, Talca, 3467987, Chile., Muñoz-Osses M; Departamento Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Avenida Libertador Bernardo O'Higgins 3363, Estación Central, Santiago, Chile., Mascayano C; Departamento Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Avenida Libertador Bernardo O'Higgins 3363, Estación Central, Santiago, Chile.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2024 Nov; Vol. 260, pp. 112689. Date of Electronic Publication: 2024 Aug 04.
DOI: 10.1016/j.jinorgbio.2024.112689
Abstrakt: In the search of new cymantrenyl- and ferrocenyl-sulfonamides as potencial inhibitors of human carbonic anhydrases (hCAs), four compounds based on N-ethyl or N-methyl benzenesulfonamide units have been obtained. These cymantrenyl (1a-b) and ferrocenyl (2a-b) derivatives were prepared by the reaction between aminobenzene sulfonamides ([NH 2 -(CH 2 ) n -(C 6 H 4 )-SO 2 -NH 2 )], where n = 1, 2) with cymantrenyl sulfonyl chloride (P1) or ferrocenyl sulfonyl chloride (P2), respectively. All compounds were characterized by conventional spectroscopic techniques and cyclic voltammetry. In the solid state, the molecular structures of compounds 1a, 1b, and 2b were determined by single-crystal X-ray diffraction. Biological evaluation as carbonic anhydrases inhibitors were carried out and showed derivatives 1b y 2b present a higher inhibition than the drug control for the Human Carbonic Anhydrase (hCA) II and IX isoforms (K I  = 7.3 nM and 5.8 nM, respectively) and behave as selective inhibition for hCA II isoform. Finally, the docking studies confirmed they share the same binding site and interactions as the known inhibitors acetazolamide (AAZ) and agree with biological studies.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodrigo Arancibia reports financial support was provided by National Agency for Research and Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: