- Title
- Discovery of 4,6-bis(2-((E)-benzylidene)hydrazinyl)pyrimidin-2-amine with antibiotic activity
- Creator
- Russell, Cecillia C.; Stevens, Andrew; McCluskey, Adam; Young, Kelly A.; Baker, Jennifer R.; McCluskey, Siobhann N.; Khazandi, Manouchehr; Pi, Hongfei; Ogunniyi, Abiodun; Page, Stephen W.; Trott, Darren J.
- Relation
- ARC.LP110200770 http://purl.org/au-research/grants/arc/LP110200770
- Relation
- ChemistryOpen Vol. 8, Issue 7, p. 896-907
- Publisher Link
- http://dx.doi.org/10.1002/open.201800241
- Publisher
- Wiley - V C H Verlag GmbH & Co. KGaA
- Resource Type
- journal article
- Date
- 2019
- Description
- Robenidine (E)‐N′‐((E)‐1‐(4‐chlorophenyl)ethylidene)‐2‐(1‐(4‐chlorophenyl)ethylidene)hydrazine‐1‐carboximidhydrazide displays methicillin‐resistant Staphyoccoccus aureus (MRSA) and vancomycin‐resistant Enterococci (VRE) MICs of 2 μg mL−1. Herein we describe the structure‐activity relationship development of a novel series of guanidine to 2‐aminopyrimidine isosteres that ameliorate the low levels of mammalian cytotoxicity in the lead compound while retaining good antibiotic activity. Removal of the 2‐NH2 pyrimidine moiety renders these analogues inactive. Introduction of a central 2‐NH2 triazine moiety saw a 10‐fold activity reduction. Phenyl to cyclohexyl isosteres were inactive. The 4‐BrPh and 4‐CH3Ph with MIC values of 2 and 4 μg mL−1, against MRSA and VRE respectively, are promising candidates for future development.
- Subject
- aminopyrimidines; antibacterial activity; robenidine; drugs discovery; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1442735
- Identifier
- uon:41781
- Identifier
- ISSN:2191-1363
- Rights
- © 201x The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
- Language
- eng
- Full Text
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