Investigation of the influence of chirality and halogen atoms on the anticancer activity of enantiopure palladium(ii) complexes derived from chiral amino-alcohol Schiff bases and 2-picolylamine†
*a
Jose V.
Cuevas-Vicario,
b
Isabel
Correia,
d
Mohammed
Enamullah,
f
Alexandra R.
Fernandes
gh
and
Abstract
In continuation of our work on the synthesis of heteroleptic enantiopure Pd(II)-complexes, four mixed-ligand enantiomeric pairs of Pd(II) complexes (J1–J8), [Pd(pic) (R or S)-N-(2,3-dihydroxypropyl)-3,5-X1,X2-salicylaldimines]NO3, (pic = 2-picolylamine; X1 = X2 = Cl, Br, I; X1/X2 = Br/Cl), were synthesized by the reaction of enantiopure halogen-substituted Schiff bases (R or S)-N-(2,3-dihydroxypropyl)-3,5-X1,X2-salicylaldimines with [Pd(pic)Cl2] and obtained as yellow precipitates. The composition and structure of the complexes were confirmed by means of elemental analyses, NMR (1H and 13C), FT-IR spectroscopy and theoretical calculations. The NMR data confirmed the stability of these complexes in DMSO. The electronic structure of the reported complexes was investigated using UV-Vis absorption and electronic circular dichroism (ECD) spectroscopy. The antiproliferative activity of the newly synthesized metal complexes was evaluated against CCRF-CEM acute lymphocytic leukemia cells and their multidrug-resistant CEM/ADR5000 subline showing IC50 values in the low-micromolar range. The two most active compounds (J4 and J6) in the assays above were selected for further biological testing, i.e. cell cycle analyses, apoptosis detection and ability to inhibit the chymotrypsin-like activity of the 20S human proteasome. Both compounds arrested the G2/M cell cycle phase in a concentration-dependent manner without inducing significant apoptosis and inhibited the above-mentioned proteolytic activity of the proteasome in the low-micromolar range.
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