2-(Pyridin-4yl)benzothiazole and Its Benzimidazole-Analogue: Biophysical and in silico Studies on Their Interaction with Urease and in vitro Anti- Helicobacter pylori Activities

Journal of the Brazilian Chemical Society

article

Pereira, Camila P.¹  Lyra, Ana C. F. de²  Oliveira, Breno G. F.¹  Nascimento, Igor J. S.²  Silva-Júnior, Edeildo F. da²  Aquino, Thiago M. de²  Sisto, Francesca³  Figueiredo, Isis M.²  Martins, Felipe T.⁴  Modolo, Luzia V.¹  Santos, Josué C. C.²  Fátima, Ângelo de¹ 

[1] Universidade Federal de Minas Gerais;Universidade Federal de Alagoas;Università degli Studi di Milano;Universidade Federal de Goiás

关键词: urease;    urease inhibitor;    benzothiazole;    benzimidazole;    drug-protein interaction;    spectroscopic techniques;   

DOI  :  10.21577/0103-5053.20220020

学科分类：内科医学

来源: SciELO

【 摘 要 】

In this study, the interaction between benzothiazole (BTA, concentration of a drug required for 50% inhibition in vitro (IC50) = 0.77 mM) and benzimidazole (BIA, IC50 = 2.14 mM) with urease was quantitatively assessed, using UV-Vis, molecular fluorescence, and circular dichroism. The results showed that both compounds interact with urease by a static fluorescence quenching mechanism with a non-fluorescent complex formation. The main forces responsible for stabilizing the supramolecular complex between BTA and urease were hydrophobic while, for BIA, van der Waals interactions and hydrogen bonds were the main ones. Urease conformation changes due to the interaction process were analyzed by circular dichroism and synchronous fluorescence. Besides, a competitive assay with substrate and inhibitors was used to evaluate the preferential urease site of interaction with BTA and BIA. Our experimental and theoretical studies supported that both, BTA and BIA, are mixed-inhibitors of ureases with a slight preference to the active site of such enzymes. Finally, both BTA and BIA showed to possess anti-Helicobacter pylori 3366 µM, respectively.

【 授权许可】

CC BY