Synthesis and structure–activity relationship of N4-benzylamine-N2-isopropyl-quinazoline-2,4-diamines derivatives as potential antibacterial agents

Jiang, Zhengyun, Hong, Weiqian, Cui, Xiping, Gao, Hongcan, Wu, Panpan, Chen, Yingshan, Shen, Ding, Yang, Yang, Zhang, Bingjie, Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192, O'Neill, Paul M., Zhao, Suqing and Zhang, Kun (2017) 'Synthesis and structure–activity relationship of N4-benzylamine-N2-isopropyl-quinazoline-2,4-diamines derivatives as potential antibacterial agents'. RSC Advances, Vol 7, Issue 82, pp. 52227-52237.

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Abstract

A series of N4-benzylamine-N2-isopropyl-quinazoline-2,4-diamine derivatives has been synthesized and tested for antibacterial activity against five bacterial strains. Twelve different substituents on the N4-benzylamine group have been investigated along with replacement of the quinazoline core (with either a benzothiophene or regioisomeric pyridopyrimidine ring systems). In order to develop structure activity relationships, all derivatives were tested for their antibacterial activities against Escherichia coli and Staphylococcus aureus via Kirby–Bauer assays and minimum inhibitory concentration assays. Eight of the most potent compounds against S. aureus and E. coli were also screened against one strain of methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis and Salmonella typhimurium to further examine their antibacterial activities. Lead compound A5 showed good activities with MICs of 3.9 μg mL−1 against E. coli, S. aureus and S. epidermidis and 7.8 μg mL−1 against MRSA. Selected front runners were also screened for their DMPK properties in vitro to assess their potential for further development.

Item Type:	Article
Subjects:	QV Pharmacology > Cardiovascular Agents. Renal Agents > QV 150 Cardiovascular agents QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 354 Penicillins QW Microbiology and Immunology > Bacteria > QW 142 Gram-positive bacteria (General) WB Practice of Medicine > Therapeutics > WB 330 Drug therapy
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1039/c7ra10352b
SWORD Depositor:	JISC Pubrouter
Depositing User:	Stacy Murtagh
Date Deposited:	17 Nov 2017 15:26
Last Modified:	16 Sep 2019 09:01
URI:	https://archive.lstmed.ac.uk/id/eprint/7827

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