In:
ChemMedChem, Wiley, Vol. 17, No. 2 ( 2022-01-19)
Abstract:
Thirty‐eight disulfides containing N ‐arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell‐free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2′‐dithiobis( N ‐(2‐fluorophenyl)acetamide) ( d7 ), 2,2′‐dithiobis( N ‐(3,5‐difluorophenyl)acetamide) ( d24 ), and 2,2′‐dithiobis( N ‐(3‐fluorophenyl)acetamide) ( d8 ) were here identified as the most active inhibitors with IC 50 of 0.074, 0.44, and 0.81 μM, showing 32‐ to 355‐fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti‐ Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.202100618
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2209649-8
SSG:
15,3
