Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives.

Autor: Mohammed SO; Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, Khartoum 11111, Sudan., El Ashry SHE; Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21568, Egypt., Khalid A; Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, Khartoum 11111, Sudan.; Substance Abuse and Toxicology Research Center, Jazan University, Jazan 45142, Saudi Arabia., Amer MR; Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21568, Egypt., Metwaly AM; Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.; Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt., Eissa IH; Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt., Elkaeed EB; Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah, Riyadh 13713, Saudi Arabia., Elshobaky A; Botany Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt., Hafez EE; Plant Protection and Biomolecular Diagnosis Department, City of Scientific Research and Technological Applications, ARADI, Alexandria 21934, Egypt.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2022 Jan 27; Vol. 27 (3). Date of Electronic Publication: 2022 Jan 27.
DOI: 10.3390/molecules27030865
Abstrakt: The urease enzyme has been an important target for the discovery of effective pharmacological and agricultural products. Thirteen regio-selectively alkylated benzimidazole-2-thione derivatives have been designed to carry the essential features of urease inhibitors. The urease enzyme was isolated from Helicobacter pylori as a recombinant urease utilizing the His-tag method. The isolated enzyme was purified and characterized using chromatographic and FPLC techniques showing a maximal activity of 200 mg/mL. Additionally, the commercial Jack bean urease was purchased and included in this study for comparative and mechanistic investigations. The designed compounds were synthesized and screened for their inhibitory activity against the two ureases. Compound 2 inhibited H. pylori and Jack bean ureases with IC 50 values of 0.11; and 0.26 mM; respectively. While compound 5 showed IC 50 values of 0.01; and 0.29 mM; respectively. Compounds 2 and 5 were docked against Helicobacter pylori urease (PDB ID: 1E9Y; resolution: 3.00 Å) and exhibited correct binding modes with free energy (ΔG) values of -9.74 and -13.82 kcal mol -1 ; respectively. Further; the in silico ADMET and toxicity properties of 2 and 5 indicated their general safeties and likeness to be used as drugs. Finally, the compounds' safety was authenticated by an in vitro cytotoxicity assay against fibroblast cells.
Databáze: MEDLINE
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