Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.

@article{Scocchera2016ChargedNA,
  title={Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.},
  author={Eric Scocchera and Stephanie Reeve and Santosh Keshipeddy and Michael N. Lombardo and Behnoush Hajian and Adrienne E. Sochia and Jeremy B. Alverson and Nigel D. Priestley and Amy C. Anderson and Dennis L Wright},
  journal={ACS medicinal chemistry letters},
  year={2016},
  volume={7 7},
  pages={
          692-6
        }
}
Although classical, negatively charged antifolates such as methotrexate possess high affinity for the dihydrofolate reductase (DHFR) enzyme, they are unable to penetrate the bacterial cell wall, rendering them poor antibacterial agents. Herein, we report a new class of charged propargyl-linked antifolates that capture some of the key contacts common to the classical antifolates while maintaining the ability to passively diffuse across the bacterial cell wall. Eight synthesized compounds exhibit… CONTINUE READING
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