The study of the reactivity of three 1-(2-dimethylaminoethyl)-1H-pyrazole derivatives of general formula [1-(CH 2 ) 2 NMe 2 }-3,5-R 2 -pzol] {where pzol represents pyrazole and R_H (1a), Me (1b) (5c)}. Compounds 4c and 5c arise from the orthometallation of the 3-phenyl ring of ligand 1c. Complex 2a has been further characterized by X-ray crystallography. Ligands and complexes were evaluated for their in vitro antimalarial against Plasmodium falciparum and cytotoxic activities against lung (A549) and breast (MDA MB231 and MCF7) cancer cellular lines. Complexes 2a-2c and 5c exhibited only moderate antimalarial activities against two P. falciparum strains (3D7 and W2). Interestingly, cytotoxicity assays revealed that the platinacycle 4c exhibits a higher toxicity than cisplatin in the three human cell lines and that the complex 2a presents a remarkable cytotoxicity and selectivity in lung (IC 50 = 3 μM) versus breast cancer cell lines (IC 50 N 20 μM). Thus, complexes 2c and 4c appear to be promising leads, creating a novel family of anticancer agents. Electrophoretic DNA migration studies in presence of the synthesized compounds have been performed, in order to get further insights into their mechanism of action.
The cyclopalladation of a series of symmetric diimines with the formula (RC 6 H 4 CHNZ) 2 , where Z = CH 2 or (CH 2 ) 2 OCH 2 and R = p-Cl, p-OMe, p-NO 2 , and o-Cl, is described. Optimal conditions to obtain the dimetalated compounds were found to be palladium(II) acetate, in toluene, at 60 °C and with a reaction time of 2−4 h. The reactivity of the dimetalated compounds with monodentate, bidentate, and bis(monodentate) Lewis bases was also studied. The cytotoxic activity of some selected compounds was evaluated against a panel of adenocarcinoma cell lines (colon HCT116 and breast MCF7 and MDA-MB231). Compounds containing the fragment NCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 N exhibited a remarkable cytotoxic activity in the three cancer cells assayed, but complexes containing the NCH 2 CH 2 N fragment showed no activity. It seems that the length and flexibility of the central saturated chain in the imine molecule, as well as its lipophilicity and hydrophilicity, explain the different cytotoxicity of the two series of coordination compounds here reported.
The synthesis of bidentate monoanionic C−N derivatives of
2-oxopropionaldehyde phenylhydrazones, compounds 3,
[Pd(2-{NHNCHC(O)Me}-3-RC6H3)Cl(PPh3)]
is described.
The structure of 3b (R = Me) was determined by X-ray
diffraction. The bond distances and
angles are similar to those reported for related metallacycles.
The distance N(2)···O(1) (2.583(7) Å) shows the existence of a strong intramolecular hydrogen bond
between the NH and
COCH3 groups. The C(9)−O(1) (1.224(9) Å),
C(8)−C(9) (1.46(1) Å), C(8)−N(1) (1.307(8)
Å),
and N1−N2 (1.325(7) Å) bond lengths indicate that 3b
exists mainly in the keto−hydrazo
form. The action of NaMeO on 3 in MeOH afforded deep
violet compounds which did not
contain chlorine atoms. The analytical data, the infrared spectra,
and the NMR studies,
including 1H−1H COSY and NOESY experiments,
showed that deprotonation of the N−H
bond took place to give 4,
[Pd(2-{NN−CHC(O)Me}-3-RC6H3)(PPh3)]
by means of an
unexpected hydrazo−azo tautomerization. The structure of
4c (R = Et) was determined by
X-ray diffraction. The C(10)−O(1) (1.32(1) Å),
C(10)−C(9) (1.37(1) Å), C(9)−N(2) (1.33(1)
Å), and N(1)−N(2) (1.25(1) Å) bond lengths indicate that
4c exists mainly in the azo−enol
form. The action of HCl (0.5 N) on the tridentate metallacycles
4 regenerated the bidentate
derivatives 3, showing the reversibility of this process.
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