Binding affinities of selected compounds 1c, 2c, 3f, and 3h with essential residues into the active site of PTR1–Leishmania protein and DHFR–TS/T. cruzi.

Entries	Compd.	Energies in binding sites (kcal mol−1)				H-interactiona
		PTR1–Leishmania		DHFR–TS–T.cruzi
		MTX 1292b	MTX 301c	C601d	C1029e	MTX 1292	C1029
1	MTX	−8.87	−7.85	−9.11	−9.54	Tyr-455 (2.85 Å), Tyr-452 (2.67 Å), Ser-385 (2.64 Å)	Asp-561 (2.83 Å), Ile-667 (2.70 Å)
2	1c	−10.13	−8.44	−10.18	−10.65	No hydrogen bonding	Arg-566 (two bindings at 2.87 Å; 2.72 Å)
3	2c	−10.16	−8.93	−10.33	−11.14	Arg-300 (2.79 Å)	Arg-566 (two bindings: 2.30 Å; 2.78 Å), Phe-601 (2.99 Å)
4	3f	−8.87	−8.79	−11.24	−10.09	No hydrogen bonding	Arg-566 (2.42 Å), Ser-553 (2.90 Å)
5	3h	−9.01	−8.89	−10.33	−10.06	Tyr-452 (2.99 Å), Tyr-452 (2.25 Å)	Arg-566 (2.41 Å), Ser-533 (2.90 Å)

^aHydrogen bond interactions.

^bBinding site in cavity 1 for methotrexate.

^cBinding site in cavity 2 for methotrexate.

^dBinding site in cavity 1 for antifolate C50 and.

^eBinding site in cavity 2 for antifolate C50.