TY - JOUR
T1 - New copper(i) complexes selective for prostate cancer cells
AU - Machado, João Franco
AU - Sequeira, Diogo A.
AU - Marques, Fernanda Marujo
AU - Piedade, M. Fátima M.
AU - Villa De Brito, Maria J.
AU - Helena Garcia, M.
AU - Fernandes, Alexandra R.
AU - Morais, Tânia S.
N1 - Fundação para a Ciência e Tecnologia (FCT) through projects UIDB/00100/2020, UID/Multi/04349/2019 and UIDB/04378/2020.
T. S. Morais thanks FCT for CEECIND 2017 Initiative for the project CEECIND/00630/2017 (acknowledging FCT, as well as POPH and FSE-European Social Fund).
J. F. Machado thanks FCT for his doctoral grant (SFRH/BD/135915/2018).
PY - 2020/9/21
Y1 - 2020/9/21
N2 - A new family of eighteen Cu(i) complexes of the general formula [Cu(PP)(LL)][BF4], where PP is a phosphane ligand and LL represents an N,O-heteroaromatic bidentate ligand, has been synthesized and fully characterized by classical analytical and spectroscopic methods. Five complexes of this series were also characterized by single crystal X-ray diffraction studies. The cytotoxicity of all compounds was evaluated in breast (MCF7) and prostate (LNCap) human cancer cells and in a normal prostate cell line (RWPE). In general, all compounds showed higher cytotoxicity for the prostate cancer cells than for the breast cells, with IC50 values in the range 0.2-2 μM after 24 h of treatment. The most cytotoxic compound, [Cu(dppe)(2-ap)][BF4] (16), where dppe = 1,2-bis(diphenylphosphano) ethane and 2-ap = 2-acetylpyridine, showed a high level of cellular internalization, generation of intracellular ROS and activation of the cell death mechanism via apoptosis/necrosis. Owing to its high cytotoxic activity for LNCap cells, being 70-fold higher than that for normal prostate cells (RWPE), complex (16) was found to be the most promising for further research in prostate cancer models.
AB - A new family of eighteen Cu(i) complexes of the general formula [Cu(PP)(LL)][BF4], where PP is a phosphane ligand and LL represents an N,O-heteroaromatic bidentate ligand, has been synthesized and fully characterized by classical analytical and spectroscopic methods. Five complexes of this series were also characterized by single crystal X-ray diffraction studies. The cytotoxicity of all compounds was evaluated in breast (MCF7) and prostate (LNCap) human cancer cells and in a normal prostate cell line (RWPE). In general, all compounds showed higher cytotoxicity for the prostate cancer cells than for the breast cells, with IC50 values in the range 0.2-2 μM after 24 h of treatment. The most cytotoxic compound, [Cu(dppe)(2-ap)][BF4] (16), where dppe = 1,2-bis(diphenylphosphano) ethane and 2-ap = 2-acetylpyridine, showed a high level of cellular internalization, generation of intracellular ROS and activation of the cell death mechanism via apoptosis/necrosis. Owing to its high cytotoxic activity for LNCap cells, being 70-fold higher than that for normal prostate cells (RWPE), complex (16) was found to be the most promising for further research in prostate cancer models.
UR - http://www.scopus.com/inward/record.url?scp=85091127383&partnerID=8YFLogxK
U2 - 10.1039/d0dt02157a
DO - 10.1039/d0dt02157a
M3 - Article
C2 - 32839796
AN - SCOPUS:85091127383
SN - 1477-9226
VL - 49
SP - 12273
EP - 12286
JO - Dalton Transactions
JF - Dalton Transactions
IS - 35
ER -
