Open Access2-(Pyridin-4yl)benzothiazole and Its Benzimidazole-Analogue: Biophysical and in silico Studies on Their Interaction with Urease and in vitro Anti-Helicobacter pylori Activities
Author(s) -
Camila Pereira,
Ana de Lyra,
Breno Germano de Freitas Oliveira,
Igor José dos Santos Nascimento,
Edeildo Ferreira da Silva-Júnior,
Thiago de Aquino,
Francesca Sisto,
Ísis Martins Figueiredo,
Felipe Terra Martins,
Luzia V. Modolo,
Josué Carinhanha Caldas Santos,
Ângelo de Fátima
Publication year - 2022
Publication title -
journal of the brazilian chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.337
H-Index - 70
eISSN - 1678-4790
pISSN - 0103-5053
DOI - 10.21577/0103-5053.20220020
Subject(s) - benzothiazole , chemistry , urease , circular dichroism , fluorescence , hydrogen bond , quenching (fluorescence) , stereochemistry , benzimidazole , enzyme , combinatorial chemistry , biochemistry , organic chemistry , molecule , physics , quantum mechanics
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-H. pylori (one reference strain and six clinical isolates) activity, presenting minimal inhibitory concentration (MIC) values ranging from 38-150 and 20-164 μM, respectively. The urease inhibitors omeprazole and hydroxyurea showed MIC values in the range of 46-185 μM and 1683-> 3366 μM, respectively.