Synthesis and antibacterial evaluation of a novel series of synthetic phenylthiazole compounds against methicillin-resistant Staphylococcus aureus (MRSA)

European Journal of Medicinal Chemistry
Haroon MohammadMohamed N Seleem

Abstract

Methicillin-resistant Staphylococcus aureus infections are a significant global health challenge in part due to the emergence of strains exhibiting resistance to nearly all classes of antibiotics. This underscores the urgent need for the rapid development of novel antimicrobials to circumvent this burgeoning problem. Previously, whole-cell screening of a library of 2,5-disubstituted thiazole compounds revealed a lead compound exhibiting potent antimicrobial activity against MRSA. The present study, conducting a more rigorous analysis of the structure-activity relationship of this compound, reveals a nonpolar, hydrophobic functional group is favored at thiazole-C2 and an ethylidenehydrazine-1-carboximidamide moiety is necessary at C5 for the compound to possess activity against MRSA. Furthermore, the MTS assay confirmed analogs 5, 22d, and 25 exhibited an improved toxicity profile (not toxic up to 40 μg/mL to mammalian cells) over the lead 1. Analysis with human liver microsomes revealed compound 5 was more metabolically stable compared to the lead compound (greater than eight-fold improvement in the half-life in human liver microsomes). Collectively the results presented demonstrate the novel thiazole derivatives synthesized wa...Continue Reading

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Citations

Sep 24, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cristina NastasăOvidiu Oniga
May 18, 2016·Journal of Medicinal Chemistry·Mohammed A SeleemAbdelrahman S Mayhoub
Feb 2, 2019·Current Topics in Medicinal Chemistry·Christophe TratratMarina Soković
Feb 21, 2021·Bioorganic & Medicinal Chemistry Letters·Bhautikkumar PatelSantosh Rudrawar
Aug 26, 2019·European Journal of Medicinal Chemistry·Mohamed M ElsebaeiAbdelrahman S Mayhoub
Feb 23, 2021·Frontiers in Microbiology·Xiufeng ZhangZhenling Zeng
Apr 2, 2018·European Journal of Medicinal Chemistry·Ahmed KotbAbdelrahman S Mayhoub
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anthi PetrouAthina Geronikaki

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