From Phenylthiazoles to Phenylpyrazoles: Broadening
the Antibacterial Spectrum toward Carbapenem-Resistant Bacteria
Posted on 2019-08-18 - 14:13
The
narrow antibacterial spectrum of phenylthiazole antibiotics was expanded
by replacing central thiazole with a pyrazole ring while maintaining
its other pharmacophoric features. The most promising derivative,
compound 23, was more potent than vancomycin against
multidrug-resistant Gram-positive clinical isolates, including vancomycin-
and linezolid-resistant methicillin-resistant Staphylococcus
aureus (MRSA), with a minimum inhibitory concentration
(MIC) value as low as 0.5 μg/mL. Moreover, compound 23 was superior to imipenem and meropenem against highly pathogenic
carbapenem-resistant strains, such as Acinetobacter
baumannii, Klebsiella pneumoniae, and Escherichia coli. In addition
to the notable biofilm inhibition activity, compound 23 outperformed both vancomycin and kanamycin in reducing the intracellular
burden of both Gram-positive and Gram-negative pathogenic bacteria.
Compound 23 cleared 90% of intracellular MRSA and 98%
of Salmonella enteritidis at 2×
the MIC. Moreover, preliminary pharmacokinetic investigations indicated
that this class of novel antibacterial compounds is highly metabolically
stable with a biological half-life of 10.5 h, suggesting a once-daily
dosing regimen.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Hammad, Ali; Abutaleb, Nader S.; Elsebaei, Mohamed M.; Norvil, Allison B.; Alswah, Mohamed; Ali, Alsagher O.; et al. (2019). From Phenylthiazoles to Phenylpyrazoles: Broadening
the Antibacterial Spectrum toward Carbapenem-Resistant Bacteria. ACS Publications. Collection. https://doi.org/10.1021/acs.jmedchem.9b00720
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (12)
AH
Ali Hammad
NA
Nader S. Abutaleb
ME
Mohamed M. Elsebaei
AN
Allison B. Norvil
MA
Mohamed Alswah
AA
Alsagher O. Ali
JA
Jelan A. Abdel-Aleem
AA
Abdelaziz Alattar
SB
Sammar A. Bayoumi
HG
Humaira Gowher
MS
Mohamed N. Seleem
AM
Abdelrahman S. Mayhoub