Fig. 1

Folate biosynthesis pathway, homology modelling and molecular docking: a DHFR-TS synthesizes dTMP while converting methylene THF to DHF which is converted back to THF by DHFR-TS. PTR1 converts H2 biopterin to H4 biopterin. PTR1 can reduce both pterins and folates. WA inhibits both PTR1 and DHFR-TS enzymes. b Superimposed image of the template T. cruzi DHFR-TS chain A (PDB ID: 3INV) shown in blue and modeled Ld DHFR-TS shown in green. c Substrate DHFA (red) binds to two active sites of Ld DHFR-TS where an electrostatic channel is formed and substrate channeling between both the active sites is observed. Competitive inhibitor MTX (blue) competes with DHFA (red) and binds to two active sites of Ld DHFR-TS. Inhibitor WA (yellow) is binding to Ld DHFR-TS enzyme by blocking the electrostatic channel. d Substrate DHFA (red), Competitive inhibitor MTX (blue) and inhibitor WA (yellow) binding to Hu DHFR enzyme. e Substrate dUMP (red), inhibitors MTX (blue) and WA (yellow) binding to Hu TS enzyme