Investigating Propargyl-Linked Antifolates in Inhibiting Bacterial and Fungal Dihydrofolate Reductase

摘要: Antimicrobial agents have been invaluable in reducing illness and death associated with bacterial infection. However, over time, bacteria evolved resistance to all major drug classes as a result of selective pressure. The advancement new compounds is therefore vital. Anderson-Wright Lab has focused on developing potent inhibitors dihydrofolate reductase (DHFR), an enzyme key cell proliferation survival, several pathogenic species. lab found that set compounds, known propargyl-linked antifolates, are DHFR both biologically effective strong pharmacokinetic properties. efficacy novel antifolates inhibiting was tested enzymatic assays three species: Candida albicans, glabrata, Klebsiella pneumoniae. In order gauge the potency results tests were referenced against assay using trimethoprim, which known, powerful inhibitor DHFR. Additionally, x-ray crystallography employed generate dimensional representation inhibitor:pathogen interactions. data from utilized deduce structural analogs most given pathogens. Knowing what specific molecular features comprise allows strive towards more ideal allow for future development increasingly antimicrobials.