Toward Broad Spectrum Dihydrofolate Reductase Inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin Resistant Staphylococcus aureus

Debjani Si
Debjani Si
Jolanta Krucinska
Jolanta Krucinska
Yongzhao Yan
Yongzhao Yan
Siyu Wang
Siyu Wang
Graham T. Holt
Graham T. Holt
Marcel S. Frenkel
Marcel S. Frenkel
Adegoke A. Ojewole
Adegoke A. Ojewole
Alexavier Estrada
Alexavier Estrada
Sherry S. Agabiti
Sherry S. Agabiti

ACS INFECTIOUS DISEASES, pp. 1896-1906, 2019.

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Abstract:

The spread of plasmid borne resistance enzymes in clinical Staphylococcus aureus isolates is rendering trimethoprim and iclaprim, both inhibitors of dihydrofolate reductase (DHFR), ineffective. Continued exploitation of these targets will require compounds that can broadly inhibit these resistance-conferring isoforms. Using a structure-ba...More

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