Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones

Thangavel Thirunavukkarasu; Hazel A Sparkes; Valentina Gandin; Cristina Marzano; Roberta Bertani; Mirto Mozzon; Anna Scettri; Francesco Demartin; Girolamo Casella; Francesco Ferrante; Alfonso Zoleo; Paolo Sgarbossa; Karuppannan Natarajan

doi:10.1016/j.ica.2024.122022

Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones

Thangavel Thirunavukkarasu, Hazel A Sparkes, Valentina Gandin, Cristina Marzano, Roberta Bertani, Mirto Mozzon, Anna Scettri, Francesco Demartin, Girolamo Casella, Francesco Ferrante, Alfonso Zoleo, Paolo Sgarbossa^*, Karuppannan Natarajan^*

^*Corresponding author for this work

School of Chemistry

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Abstract

Three new coordination complexes of Cu(II) ions made from two hydrazone ligands, 7 -chloro2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL1) and 6-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL2) have been synthesized and fully characterized by spectroscopic techniques. Their crystal and molecular structures revealed
distorted square pyramidal mononuclear complexes: [(L1)Cu(H₂O)₂](NO3)·3H₂O, 1(NO₃), [(L2)Cu(H₂O)₂](NO₃)·2H₂O·CH₃OH, 2(NO₃), and [(L2)Cu(NO₃)[CH₃OH)]·2CH₃OH, 3, comprising the ligand (L1 and L2) in tridentate fashion (ONO) with two water molecules in 1⁺and 2⁺, and a single methanol molecule and a nitrate ion in 3 in their respective copper coordination spheres. EPR spectra in frozen methanol revealed the occurrence of several species arising from different coordination environments. A detailed DFT investigation on the energetics of solvents exchange (H₂O, MeOH, and DMSO) and simulation of the EPR parameters showed that the exchange processes occur easily in solution. The value gz indicated the occurrence of a dimeric aggregate for 2⁺. The new copper complexes exhibited a noticeable antiproliferative activity with IC₅₀ values in the micromolar range against HCT-15, H157, BxPC3, PNS-1, and
A431 cell lines and they were found to be 3-fold more effective than cisplatin against pancreatic PSN-1 cell lines. Cross-resistance tests on A2780 and LoVo cancer cell lines and the corresponding multidrug or oxaliplatin resistant sublines showed that complexes 1(NO₃) and 2(NO₃) were equally cytotoxic to sensitive and resistant cells, thus overcoming multidrug and oxaliplatin resistance.

Original language	English
Article number	122022
Number of pages	11
Journal	Inorganica Chimica Acta
Volume	566
Early online date	15 Mar 2024
DOIs	https://doi.org/10.1016/j.ica.2024.122022
Publication status	Published - 1 Jun 2024

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© 2024 The Author(s)

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Thirunavukkarasu, T., Sparkes, H. A., Gandin, V., Marzano, C., Bertani, R., Mozzon, M., Scettri, A., Demartin, F., Casella, G., Ferrante, F., Zoleo, A., Sgarbossa, P., & Natarajan, K. (2024). Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones. Inorganica Chimica Acta, 566, Article 122022. https://doi.org/10.1016/j.ica.2024.122022

@article{6de51c6eea5e4e22a021219b682a2376,

title = "Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones",

abstract = "Three new coordination complexes of Cu(II) ions made from two hydrazone ligands, 7 -chloro2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL1) and 6-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL2) have been synthesized and fully characterized by spectroscopic techniques. Their crystal and molecular structures revealed distorted square pyramidal mononuclear complexes: [(L1)Cu(H2O)2](NO3)·3H2O, 1(NO3), [(L2)Cu(H2O)2](NO3)·2H2O·CH3OH, 2(NO3), and [(L2)Cu(NO3)[CH3OH)]·2CH3OH, 3, comprising the ligand (L1 and L2) in tridentate fashion (ONO) with two water molecules in 1+and 2+, and a single methanol molecule and a nitrate ion in 3 in their respective copper coordination spheres. EPR spectra in frozen methanol revealed the occurrence of several species arising from different coordination environments. A detailed DFT investigation on the energetics of solvents exchange (H2O, MeOH, and DMSO) and simulation of the EPR parameters showed that the exchange processes occur easily in solution. The value gz indicated the occurrence of a dimeric aggregate for 2+. The new copper complexes exhibited a noticeable antiproliferative activity with IC50 values in the micromolar range against HCT-15, H157, BxPC3, PNS-1, and A431 cell lines and they were found to be 3-fold more effective than cisplatin against pancreatic PSN-1 cell lines. Cross-resistance tests on A2780 and LoVo cancer cell lines and the corresponding multidrug or oxaliplatin resistant sublines showed that complexes 1(NO3) and 2(NO3) were equally cytotoxic to sensitive and resistant cells, thus overcoming multidrug and oxaliplatin resistance.",

author = "Thangavel Thirunavukkarasu and Sparkes, \{Hazel A\} and Valentina Gandin and Cristina Marzano and Roberta Bertani and Mirto Mozzon and Anna Scettri and Francesco Demartin and Girolamo Casella and Francesco Ferrante and Alfonso Zoleo and Paolo Sgarbossa and Karuppannan Natarajan",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = jun,

day = "1",

doi = "10.1016/j.ica.2024.122022",

language = "English",

volume = "566",

journal = "Inorganica Chimica Acta",

issn = "0020-1693",

publisher = "Elsevier B.V.",

}

Thirunavukkarasu, T, Sparkes, HA, Gandin, V, Marzano, C, Bertani, R, Mozzon, M, Scettri, A, Demartin, F, Casella, G, Ferrante, F, Zoleo, A, Sgarbossa, P & Natarajan, K 2024, 'Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones', Inorganica Chimica Acta, vol. 566, 122022. https://doi.org/10.1016/j.ica.2024.122022

Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones. / Thirunavukkarasu, Thangavel; Sparkes, Hazel A; Gandin, Valentina et al.
In: Inorganica Chimica Acta, Vol. 566, 122022, 01.06.2024.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones

AU - Thirunavukkarasu, Thangavel

AU - Sparkes, Hazel A

AU - Gandin, Valentina

AU - Marzano, Cristina

AU - Bertani, Roberta

AU - Mozzon, Mirto

AU - Scettri, Anna

AU - Demartin, Francesco

AU - Casella, Girolamo

AU - Ferrante, Francesco

AU - Zoleo, Alfonso

AU - Sgarbossa, Paolo

AU - Natarajan, Karuppannan

PY - 2024/6/1

Y1 - 2024/6/1

N2 - Three new coordination complexes of Cu(II) ions made from two hydrazone ligands, 7 -chloro2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL1) and 6-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL2) have been synthesized and fully characterized by spectroscopic techniques. Their crystal and molecular structures revealed distorted square pyramidal mononuclear complexes: [(L1)Cu(H2O)2](NO3)·3H2O, 1(NO3), [(L2)Cu(H2O)2](NO3)·2H2O·CH3OH, 2(NO3), and [(L2)Cu(NO3)[CH3OH)]·2CH3OH, 3, comprising the ligand (L1 and L2) in tridentate fashion (ONO) with two water molecules in 1+and 2+, and a single methanol molecule and a nitrate ion in 3 in their respective copper coordination spheres. EPR spectra in frozen methanol revealed the occurrence of several species arising from different coordination environments. A detailed DFT investigation on the energetics of solvents exchange (H2O, MeOH, and DMSO) and simulation of the EPR parameters showed that the exchange processes occur easily in solution. The value gz indicated the occurrence of a dimeric aggregate for 2+. The new copper complexes exhibited a noticeable antiproliferative activity with IC50 values in the micromolar range against HCT-15, H157, BxPC3, PNS-1, and A431 cell lines and they were found to be 3-fold more effective than cisplatin against pancreatic PSN-1 cell lines. Cross-resistance tests on A2780 and LoVo cancer cell lines and the corresponding multidrug or oxaliplatin resistant sublines showed that complexes 1(NO3) and 2(NO3) were equally cytotoxic to sensitive and resistant cells, thus overcoming multidrug and oxaliplatin resistance.

AB - Three new coordination complexes of Cu(II) ions made from two hydrazone ligands, 7 -chloro2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL1) and 6-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL2) have been synthesized and fully characterized by spectroscopic techniques. Their crystal and molecular structures revealed distorted square pyramidal mononuclear complexes: [(L1)Cu(H2O)2](NO3)·3H2O, 1(NO3), [(L2)Cu(H2O)2](NO3)·2H2O·CH3OH, 2(NO3), and [(L2)Cu(NO3)[CH3OH)]·2CH3OH, 3, comprising the ligand (L1 and L2) in tridentate fashion (ONO) with two water molecules in 1+and 2+, and a single methanol molecule and a nitrate ion in 3 in their respective copper coordination spheres. EPR spectra in frozen methanol revealed the occurrence of several species arising from different coordination environments. A detailed DFT investigation on the energetics of solvents exchange (H2O, MeOH, and DMSO) and simulation of the EPR parameters showed that the exchange processes occur easily in solution. The value gz indicated the occurrence of a dimeric aggregate for 2+. The new copper complexes exhibited a noticeable antiproliferative activity with IC50 values in the micromolar range against HCT-15, H157, BxPC3, PNS-1, and A431 cell lines and they were found to be 3-fold more effective than cisplatin against pancreatic PSN-1 cell lines. Cross-resistance tests on A2780 and LoVo cancer cell lines and the corresponding multidrug or oxaliplatin resistant sublines showed that complexes 1(NO3) and 2(NO3) were equally cytotoxic to sensitive and resistant cells, thus overcoming multidrug and oxaliplatin resistance.

U2 - 10.1016/j.ica.2024.122022

DO - 10.1016/j.ica.2024.122022

M3 - Article (Academic Journal)

SN - 0020-1693

VL - 566

JO - Inorganica Chimica Acta

JF - Inorganica Chimica Acta

M1 - 122022

ER -

Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3- carbaldehyde-2-furoyl-hydrazones

Abstract

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