TY - JOUR

T1 - Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes

AU - Geyl, Kirill K.

AU - Baykov, Sergey V.

AU - Kalinin, Stanislav A.

AU - Bunev, Alexandr S.

AU - Troshina, Marina A.

AU - Sharonova, Tatiana V.

AU - Skripkin, Mikhail Yu

AU - Kasatkina, Svetlana O.

AU - Presnukhina, Sofia I.

AU - Shetnev, Anton A.

AU - Krasavin, Mikhail Yu

AU - Boyarskiy, Vadim P.

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/2/16

Y1 - 2022/2/16

N2 - Relying on a recently suggested protocol that furnishes convenient access to variously substituted 2-pyridyl ureas, twelve hitherto unknown Cu(II) complexes have been synthesized in the present work and their structures were evaluated by elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two structural motifs ([Cu(L)2Cl]+[Cl]− or (Cu(L)2Cl2 ) depending on the substitution pattern on the 2-pyridine fragment were revealed. In addition, antiproliferative action of the obtained compounds have been investigated against lung cancer cell lines (A549, NCI-H460, NCIH1975), and healthy WI-26 VA4 cells were used to monitor non-specific cytotoxicity. Two nitro-group substituted complexes Cu(U3)2Cl2 (IC50 = 39.6 ± 4.5 µM) and Cu(U11)2Cl2 (IC50 = 33.4 ± 3.8 µM) demonstrate enhanced activity against the drug resistant NCI-H1975 cells with moderate selectivity toward normal WI-26 VA4 cells. The antiproliferative mechanism of cell death underlying the growth inhibitory effect of the synthesized complexes was studied via additional experiments, including the cell cycle analysis and the apoptosis induction test. Reassuringly, certain 2-pyridyl urea-based Cu(II) complexes exerted cell line-specific antiproliferative effect which renders them valuable starting points for further unveiling the anticancer potential of this class of coordination compounds.

AB - Relying on a recently suggested protocol that furnishes convenient access to variously substituted 2-pyridyl ureas, twelve hitherto unknown Cu(II) complexes have been synthesized in the present work and their structures were evaluated by elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two structural motifs ([Cu(L)2Cl]+[Cl]− or (Cu(L)2Cl2 ) depending on the substitution pattern on the 2-pyridine fragment were revealed. In addition, antiproliferative action of the obtained compounds have been investigated against lung cancer cell lines (A549, NCI-H460, NCIH1975), and healthy WI-26 VA4 cells were used to monitor non-specific cytotoxicity. Two nitro-group substituted complexes Cu(U3)2Cl2 (IC50 = 39.6 ± 4.5 µM) and Cu(U11)2Cl2 (IC50 = 33.4 ± 3.8 µM) demonstrate enhanced activity against the drug resistant NCI-H1975 cells with moderate selectivity toward normal WI-26 VA4 cells. The antiproliferative mechanism of cell death underlying the growth inhibitory effect of the synthesized complexes was studied via additional experiments, including the cell cycle analysis and the apoptosis induction test. Reassuringly, certain 2-pyridyl urea-based Cu(II) complexes exerted cell line-specific antiproliferative effect which renders them valuable starting points for further unveiling the anticancer potential of this class of coordination compounds.

KW - Anti-cancer drugs

KW - Cytotoxicity

KW - Lung cancer

KW - Metal complexes

KW - Ureas

KW - metal complexes

KW - GOLD

KW - DESIGN

KW - PYRIDINE

KW - PLATINUM

KW - CRYSTAL-STRUCTURES

KW - VIBRATIONAL-SPECTRA

KW - NI(II)

KW - lung cancer

KW - anti-cancer drugs

KW - ureas

KW - DERIVATIVES

KW - cytotoxicity

KW - METAL-COMPLEXES

KW - CHLORIDE

UR - http://www.scopus.com/inward/record.url?scp=85125038158&partnerID=8YFLogxK

UR - https://www.mdpi.com/2227-9059/10/2/461

UR - https://www.mendeley.com/catalogue/3cd6005d-ed6f-3a9f-9dc3-b8c41371073d/

U2 - 10.3390/biomedicines10020461

DO - 10.3390/biomedicines10020461

M3 - Article

AN - SCOPUS:85125038158

VL - 10

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 2

M1 - 461

ER -