TY - JOUR
T1 - 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
AU - Rudbari, Hadi Amiri
AU - Kordestani, Nazanin
AU - Cuevas-Vicario, José V.
AU - Zhou, Min
AU - Efferth, Thomas
AU - Correia, Isabel
AU - Schirmeister, Tanja
AU - Barthels, Fabian
AU - Enamullah, Mohammed
AU - Fernandes, Alexandra R.
AU - Micale, Nicola
N1 - Funding Information:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT#
The authors are grateful to the Research Council of the University of Isfahan for the financial support of this work. This research has made use of the high-performance computing resources of the Castilla y León Supercomputing Center (SCAYLE, https://www.scayle.es), financed by FEDER (Fondo Europeo de Desarrollo Regional). This work is also financed by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB.
Publisher Copyright:
© 2022 The Royal Society of Chemistry
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85127688138&partnerID=8YFLogxK
U2 - 10.1039/d2nj00321j
DO - 10.1039/d2nj00321j
M3 - Article
AN - SCOPUS:85127688138
SN - 1144-0546
VL - 46
SP - 6470
EP - 6483
JO - New Journal of Chemistry
JF - New Journal of Chemistry
IS - 14
ER -