A new series of trimethoprim (TMP) analogs containing amide bonds (1â??6) have been\nsynthesized. Molecular docking, as well as dihydrofolate reductase (DHFR) inhibition assay were\nused to confirm their affinity to bind dihydrofolate reductase enzyme. Data from the ethidium\ndisplacement test showed their DNA-binding capacity. Tests confirming the possibility of DNA\nbinding in a minor groove as well as determination of the association constants were performed using\ncalf thymus DNA, T4 coliphage DNA, poly (dA-dT)2 and poly (dG-dC)2. Additionally, the mechanism\nof action of the new compounds was studied. In conclusion, some of our new analogs inhibited\nDHFR activity more strongly than TMP did, which confirms, that the addition of amide bonds into\nthe analogs of TMP increases their affinity towards DHFR.
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