Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of antimalarial activities of new pyrazolylpyrazoline derivatives against infected mice. Further evaluation of and against chloroquine-resistant strain (RKL9) of showed higher potency than chloroquine. antileishmanial activity testing against promastigote and amastigote forms indicated that , and possessed promising activity compared to miltefosine and amphotericin B deoxycholate. Moreover, antileishmanial activity reversal of the active compounds folic and folinic acids showed comparable results to the positive control trimethoprim, indicating an antifolate mechanism targeting leishmanial DHFR and PTR1. The compounds were non-toxic at 125, 250 and 500 mg/kg. In addition, docking of the most active compound against putative malarial target -DHFR-TS and leishmanial PTR1 rationalised the observed activities. Molecular dynamics simulations confirmed a stable and high potential binding of against leishmanial PTR1.