Two pyrazolone-based hydrazones H
2
L′
[in general,
H
2
L′; in detail,
H
2
L
1
= 5-methyl-2-phenyl-4-(2-phenyl-1-(2-(4-(trifluoromethyl)phenyl)hydrazineyl)ethyl)-2,4-dihydro-3
H
-pyrazol-3-one,
H
2
L
2
= (
Z
)-5-methyl-2-phenyl-4-(2-phenyl-1-(2-(pyridin-2-yl)hydrazineyl)ethylidene)-2,4-dihydro-3
H
-pyrazol-3-one] were reacted with Zn(II) and Cu(II) acceptors
affording the complexes [Zn(HL
1
)
2
(MeOH)
2
], [Cu(HL
1
)
2
], and [M(HL
2
)
2
] (M = Cu or Zn). X-ray and DFT studies showed the free
proligands to exist in the N–H,N–H tautomeric form and
that in [Zn(HL
1
)
2
(MeOH)
2
], zinc is
six-coordinated by the N,O-chelated (HL
1
) ligand and other
two oxygen atoms of coordinated methanol molecules, while [Cu(HL
1
)
2
] adopts a square planar geometry with the two
(HL
1
) ligands in anti-conformation. Finally, the [M(HL
2
)
2
] complexes are octahedral with the two (HL
2
) ligands acting as κ-O,N,N-donors in planar conformation.
Both the proligands and metal complexes were tested against the parasite
Trypanosoma brucei
and Balb3T3 cells. The Zn(II)
complexes were found to be very powerful, more than the starting proligands,
while maintaining a good safety level. In detail,
H
2
L
1
and its
Zn(II) complex have high selective index (55 and >100, respectively)
against
T. brucei
compared to the mammalian
Balb/3T3 reference cells. These results encouraged the researchers
to investigate the mechanism of action of these compounds that have
no structural relations with the already known drugs used against
T. brucei
. Interestingly, the analysis of NTP and
dNTP pools in
T. brucei
treated by
H
2
L
1
and its Zn(II) complex showed that the drugs had a strong
impact on the CTP pools, making it likely that CTP synthetase is the
targeted enzyme.