An in silico study including molecular docking, molecular dynamics simulations and MM-PBSA calculations was performed to investigate if 7 benzo[a]phenazines previously evaluated against malaria parasites, would be able to bind to the DHFR domain of the bifunctional enzyme Dihydrofolate Reductase-Thymidylate Synthase of P. falciparum (PfDHFR-TS). The results showed that all ligands were able to form stable complexes inside the DHFR active site of PfDHFR-TS, similarly to the pyrimethamine analogue, and DHFR inhibitor, BT1. It was also shown that these ligands can be employed as precursors in the computer aided drug design of new antimalarial PfDHFR-TS inhibitors.