A Tridentate Cu(II) Complex with a 2-(4′-Aminophenyl)Benzothiazole Derivative: Crystal Structure and Biological Evaluation for Anticancer Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Description of the Structure
2.3. EPR Analysis
2.4. DNA Binding Studies
2.4.1. Absorption Titration Studies
2.4.2. Circular Dichroism
2.4.3. Ethidium Bromide Competitive Studies
2.4.4. Thermal Denaturation Studies
2.4.5. Viscometry
2.5. Biological Evaluation
2.5.1. In Vitro Cytotoxicity
2.5.2. Cellular Uptake
2.5.3. Intracellular ROS Levels
2.5.4. Cell Cycle Analysis and Apoptosis Assessment
3. Experimental
3.1. Materials and Methods
3.2. Synthesis and Characterization
3.3. Synthesis of Complex Cu-1
3.4. X-ray Crystal Structure Determination
3.5. DNA Binding Studies
3.5.1. Absorption Titration Studies
3.5.2. Thermal Denaturation Studies
3.5.3. Circular Dichroism
3.5.4. Competitive Binding Experiments in the Presence of Ethidium Bromide
3.5.5. Viscosity Studies
3.6. In Vitro Investigation
3.6.1. MTT Viability Assay
3.6.2. Cellular Uptake by Confocal Microscopy
3.6.3. ROS Generation Detection Assay
3.6.4. Cell Cycle Analysis
3.6.5. Annexin V–PI Apoptosis Assay
3.6.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Dollwet, H.H.A.; Sorenson, J.R.J. Historic uses of copper compounds in medicine. In Trace Elements in Medicine; The Humana Press Inc.: Totowa, NJ, USA, 1985; pp. 80–87. [Google Scholar]
- Brewer, G.J. Copper in medicine. Curr. Opin. Chem. Biol. 2003, 7, 207–212. [Google Scholar] [CrossRef] [PubMed]
- Lebon, F.; Boggetto, N.; Ledecq, M.; Durant, F.; Benatallah, Z.; Sicsic, S.; Lapouyade, R.; Kahn, O.; Mouithys-Mickalad, A.; Deby-Dupont, G.; et al. Metal-organic compounds: A new approach for drug discovery. N1-(4-methyl-2-pyridyl)-2,3,6-trimethoxybenzamide copper(II) complex as an inhibitor of human immunodeficiency virus 1 protease. Biochem. Pharmacol. 2002, 63, 1863–1873. [Google Scholar] [CrossRef] [PubMed]
- Roch-Arveiller, M.; Huy, D.P.; Maman, L.; Giroud, J.P.; Sorenson, J.R. Non-steroidal anti-inflammatory drug-copper complex modulation of polymorphonuclear leukocyte migration. Biochem. Pharmacol. 1990, 39, 569–574. [Google Scholar] [CrossRef]
- Iqbal, M.S.; Khurshid, S.J.; Iqbal, M.Z. Antibacterial activity of copper-amino acid complexes. J. Pak. Med. Assoc. 1990, 40, 221–222. [Google Scholar]
- Weder, J.E.; Hambley, T.W.; Kennedy, B.J.; Lay, P.A.; MacLachlan, D.; Bramley, R.; Delfs, C.D.; Murray, K.S.; Moubaraki, B.; Warwick, B.; et al. Anti-Inflammatory Dinuclear Copper(II) Complexes with Indomethacin. Synthesis, Magnetism and EPR Spectroscopy. Crystal Structure of the N,N-Dimethylformamide Adduct. Inorg. Chem. 1999, 38, 1736–1744. [Google Scholar] [CrossRef] [PubMed]
- Szymanski, P.; Fraczek, T.; Markowicz, M.; Mikiciuk-Olasik, E. Development of copper based drugs, radiopharmaceuticals and medical materials. Biometals 2012, 25, 1089–1112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaal, A.; Orgovan, G.; Mihucz, V.G.; Pape, I.; Ingerle, D.; Streli, C.; Szoboszlai, N. Metal transport capabilities of anticancer copper chelators. J. Trace Elem. Med. Biol. 2018, 47, 79–88. [Google Scholar] [CrossRef]
- Volarevic, V.; Djokovic, B.; Jankovic, M.G.; Harrell, C.R.; Fellabaum, C.; Djonov, V.; Arsenijevic, N. Molecular mechanisms of cisplatin-induced nephrotoxicity: A balance on the knife edge between renoprotection and tumor toxicity. J. Biomed. Sci. 2019, 26, 25. [Google Scholar] [CrossRef] [Green Version]
- McWhinney, S.R.; Goldberg, R.M.; McLeod, H.L. Platinum neurotoxicity pharmacogenetics. Mol. Cancer Ther. 2009, 8, 10–16. [Google Scholar] [CrossRef] [Green Version]
- Wheate, N.J.; Walker, S.; Craig, G.E.; Oun, R. The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans. 2010, 39, 8113–8127. [Google Scholar] [CrossRef] [Green Version]
- Qin, Q.P.; Meng, T.; Tan, M.X.; Liu, Y.C.; Luo, X.J.; Zou, B.Q.; Liang, H. Synthesis, crystal structure and biological evaluation of a new dasatinib copper(II) complex as telomerase inhibitor. Eur. J. Med. Chem. 2018, 143, 1597–1603. [Google Scholar] [CrossRef]
- Molinaro, C.; Martoriati, A.; Pelinski, L.; Cailliau, K. Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II. Cancers 2020, 12, 2863. [Google Scholar] [CrossRef]
- Fatfat, M.; Merhi, R.A.; Rahal, O.; Stoyanovsky, D.A.; Zaki, A.; Haidar, H.; Kagan, V.E.; Gali-Muhtasib, H.; Machaca, K. Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species. BMC Cancer 2014, 14, 527. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sangeetha, S.; Murali, M. Non-covalent DNA binding, protein interaction, DNA cleavage and cytotoxicity of [Cu(quamol)Cl].H(2)O. Int. J. Biol. Macromol. 2018, 107, 2501–2511. [Google Scholar] [CrossRef] [PubMed]
- Marzano, C.; Pellei, M.; Tisato, F.; Santini, C. Copper complexes as anticancer agents. Anticancer Agents Med. Chem. 2009, 9, 185–211. [Google Scholar] [CrossRef] [PubMed]
- Han, Y.; Shen, T.; Jiang, W.; Xia, Q.; Liu, C. DNA cleavage mediated by copper superoxide dismutase via two pathways. J. Inorg. Biochem. 2007, 101, 214–224. [Google Scholar] [CrossRef]
- Bruijnincx, P.C.; Sadler, P.J. New trends for metal complexes with anticancer activity. Curr. Opin. Chem. Biol. 2008, 12, 197–206. [Google Scholar] [CrossRef] [Green Version]
- Chavez-Gonzalez, A.; Centeno-Llanos, S.; Moreno-Lorenzana, D.; Sandoval-Esquivel, M.A.; Aviles-Vazquez, S.; Bravo-Gomez, M.E.; Ruiz-Azuara, L.; Ayala-Sanchez, M.; Torres-Martinez, H.; Mayani, H. Casiopeina III-Ea, a copper-containing small molecule, inhibits the in vitro growth of primitive hematopoietic cells from chronic myeloid leukemia. Leuk. Res. 2017, 52, 8–19. [Google Scholar] [CrossRef]
- Lucaciu, R.L.; Hangan, A.C.; Sevastre, B.; Oprean, L.S. Metallo-Drugs in Cancer Therapy: Past, Present and Future. Molecules 2022, 27, 6485. [Google Scholar] [CrossRef]
- Alemon-Medina, R.; Brena-Valle, M.; Munoz-Sanchez, J.L.; Gracia-Mora, M.I.; Ruiz-Azuara, L. Induction of oxidative damage by copper-based antineoplastic drugs (Casiopeinas). Cancer Chemother. Pharmacol. 2007, 60, 219–228. [Google Scholar] [CrossRef]
- Mavroidi, B.; Sagnou, M.; Stamatakis, K.; Paravatou-Petsotas, M.; Pelecanou, M.; Methenitis, C. Palladium(II) and platinum(II) complexes of derivatives of 2-(4′-aminophenyl)benzothiazole as potential anticancer agents. Inorg. Chim. Acta 2016, 444, 63–75. [Google Scholar] [CrossRef]
- Tzanopoulou, S.; Sagnou, M.; Paravatou-Petsotas, M.; Gourni, E.; Loudos, G.; Xanthopoulos, S.; Lafkas, D.; Kiaris, H.; Varvarigou, A.; Pirmettis, I.C.; et al. Evaluation of Re and (99m)Tc complexes of 2-(4′-aminophenyl)benzothiazole as potential breast cancer radiopharmaceuticals. J. Med. Chem. 2010, 53, 4633–4641. [Google Scholar] [CrossRef]
- Jakusch, T.; Hassoon, A.A.; Kiss, T. Characterization of copper(II) specific pyridine containing ligands: Potential metallophores for Alzheimer’s disease therapy. J. Inorg. Biochem. 2022, 228, 111692. [Google Scholar] [CrossRef]
- Halevas, E.; Pekou, A.; Papi, R.; Mavroidi, B.; Hatzidimitriou, A.G.; Zahariou, G.; Litsardakis, G.; Sagnou, M.; Pelecanou, M.; Pantazaki, A.A. Synthesis, physicochemical characterization and biological properties of two novel Cu(II) complexes based on natural products curcumin and quercetin. J. Inorg. Biochem. 2020, 208, 111083. [Google Scholar] [CrossRef]
- Halevas, E.; Mitrakas, A.; Mavroidi, B.; Athanasiou, D.; Gkika, P.; Antoniou, K.; Samaras, G.; Lialiaris, E.; Hatzidimitriou, A.; Pantazaki, A.; et al. Structurally characterized copper-chrysin complexes display genotoxic and cytotoxic activity in human cells. Inorg. Chim. Acta 2021, 515, 120062. [Google Scholar] [CrossRef]
- Stoll, S.; Schweiger, A. EasySpin, a comprehensive software package for spectral simulation and analysis in EPR. J. Magn. Reason. 2006, 178, 42–55. [Google Scholar] [CrossRef]
- Peisach, J.; Blumberg, W.E. Structural implications derived from the analysis of electron paramagnetic resonance spectra of natural and artificial copper proteins. Arch. Biochem. Biophys. 1974, 165, 691–708. [Google Scholar] [CrossRef] [PubMed]
- Reichmann, M.E.; Rice, S.A.; Thomas, C.A.; Doty, P. A Further Examination of the Molecular Weight and Size of Desoxypentose Nucleic Acid. J. Am. Chem. Soc. 1954, 76, 3047–3053. [Google Scholar] [CrossRef]
- Sunita, M.; Padmaja, M.; Anupama, B.; Kumari, C.G. Synthesis, characterization, DNA binding and cleavage studies of mixed-ligand Cu(II) complexes of 2,6-bis(benzimidazol-2-yl)pyridine. J. Fluoresc. 2012, 22, 1003–1012. [Google Scholar] [CrossRef]
- Joseph, J.; Janaki, G.B. Copper complexes bearing 2-aminobenzothiazole derivatives as potential antioxidant: Synthesis, characterization. J. Photochem. Photobiol. B 2016, 162, 86–92. [Google Scholar] [CrossRef]
- Joseph, J.; Boomadevi Janaki, G.; Nagashri, K.; Joseyphus, R.S. Antimicrobial, antioxidant and SOD activities of copper(II) complexes derived from 2-aminobenzothiazole derivatives. J. Coord. Chem. 2016, 70, 242–260. [Google Scholar] [CrossRef]
- Vamsikrishna, N.; Kumar, M.P.; Tejaswi, S.; Rambabu, A.; Shivaraj. DNA Binding, Cleavage and Antibacterial Activity of Mononuclear Cu(II), Ni(II) and Co(II) Complexes Derived from Novel Benzothiazole Schiff Bases. J. Fluoresc. 2016, 26, 1317–1329. [Google Scholar] [CrossRef]
- Mallam, A.L.; Sidote, D.J.; Lambowitz, A.M. Molecular insights into RNA and DNA helicase evolution from the determinants of specificity for a DEAD-box RNA helicase. eLife 2014, 3, e04630. [Google Scholar] [CrossRef] [PubMed]
- Kuwabara, M.; Yoon, C.; Goyne, T.; Thederahn, T.; Sigman, D.S. Nuclease activity of 1, 10-phenanthroline-copper ion: Reaction with CGCGAATTCGCG and its complexes with netropsin and EcoRI. Biochemistry 1986, 25, 7401–7408. [Google Scholar] [CrossRef] [PubMed]
- Pakravan, P.; Masoudian, S. Study on the Interaction between Isatin-beta-Thiosemicarbazone and Calf Thymus DNA by Spectroscopic Techniques. Iran. J. Pharm. Res. 2015, 14, 111–123. [Google Scholar]
- Loganathan, R.; Ramakrishnan, S.; Suresh, E.; Palaniandavar, M.; Riyasdeen, A.; Akbarsha, M.A. Mixed ligand mu-phenoxo-bridged dinuclear copper(II) complexes with diimine co-ligands: Efficient chemical nuclease and protease activities and cytotoxicity. Dalton Trans. 2014, 43, 6177–6194. [Google Scholar] [CrossRef] [PubMed]
- Li, G.Y.; Du, K.J.; Wang, J.Q.; Liang, J.W.; Kou, J.F.; Hou, X.J.; Ji, L.N.; Chao, H. Synthesis, crystal structure, DNA interaction and anticancer activity of tridentate copper(II) complexes. J. Inorg. Biochem. 2013, 119, 43–53. [Google Scholar] [CrossRef] [PubMed]
- Lyng, R.; Rodger, A.; Norden, B. The CD of ligand-DNA systems. 2. Poly(dA-dT) B-DNA. Biopolymers 1992, 32, 1201–1214. [Google Scholar] [CrossRef] [PubMed]
- Lyng, R.; Rodger, A.; Norden, B. The CD of ligand-DNA systems. I. Poly(dG-dC) B-DNA. Biopolymers 1991, 31, 1709–1720. [Google Scholar] [CrossRef] [PubMed]
- LePecq, J.B.; Paoletti, C. A fluorescent complex between ethidium bromide and nucleic acids. Physical-chemical characterization. J. Mol. Biol. 1967, 27, 87–106. [Google Scholar] [CrossRef]
- Gaugain, B.; Barbet, J.; Capelle, N.; Roques, B.P.; Le Pecq, J.B. DNA Bifunctional intercalators. 2. Fluorescence properties and DNA binding interaction of an ethidium homodimer and an acridine ethidium heterodimer. Biochemistry 1978, 17, 5078–5088. [Google Scholar] [CrossRef]
- Banerjee, A.; Singh, J.; Dasgupta, D. Fluorescence spectroscopic and calorimetry based approaches to characterize the mode of interaction of small molecules with DNA. J. Fluoresc. 2013, 23, 745–752. [Google Scholar] [CrossRef]
- Mergny, J.L.; Lacroix, L. Analysis of thermal melting curves. Oligonucleotides 2003, 13, 515–537. [Google Scholar] [CrossRef]
- Matiadis, D.; Mavroidi, B.; Panagiotopoulou, A.; Methenitis, C.; Pelecanou, M.; Sagnou, M. (E)-1-(4-Ethoxycarbonylphenyl)-5-(3,4-dimethoxyphenyl)-3-(3,4-dimethoxystyryl)-2-pyrazoline: Synthesis, Characterization, DNA-Interaction and Evaluation of Activity Against Drug-Resistant Cell Lines. Molbank 2020, 2020, M1114. [Google Scholar] [CrossRef] [Green Version]
- Bravo-Anaya, L.M.; Rinaudo, M.; Martinez, F.A.S. Conformation and Rheological Properties of Calf-Thymus DNA in Solution. Polymers 2016, 8, 51. [Google Scholar] [CrossRef] [Green Version]
- Saraswathi, S.K.; Karunakaran, V.; Maiti, K.K.; Joseph, J. DNA Condensation Triggered by the Synergistic Self-Assembly of Tetraphenylethylene-Viologen Aggregates and CT-DNA. Front. Chem. 2021, 9, 716771. [Google Scholar] [CrossRef]
- Shokohi-Pour, Z.; Chiniforoshan, H.; Momtazi-Borojeni, A.A.; Notash, B. A novel Schiff base derived from the gabapentin drug and copper (II) complex: Synthesis, characterization, interaction with DNA/protein and cytotoxic activity. J. Photochem. Photobiol. B 2016, 162, 34–44. [Google Scholar] [CrossRef] [Green Version]
- Fox, K.R. Evaluation of Drug–Nucleic Acid Interactions by Thermal Melting Curves. In Drug-DNA Interaction Protocols; Humana Press: Totowa, NJ, USA, 1997; Volume 90. [Google Scholar]
- He, J.; Hu, P.; Wang, Y.J.; Tong, M.L.; Sun, H.; Mao, Z.W.; Ji, L.N. Double-strand DNA cleavage by copper complexes of 2,2′-dipyridyl with guanidinium/ammonium pendants. Dalton Trans. 2008, 24, 3207–3214. [Google Scholar] [CrossRef] [PubMed]
- Gomez-Machuca, H.; Quiroga-Campano, C.; Zapata-Torres, G.; Jullian, C. Influence of DMbetaCD on the Interaction of Copper(II) Complex of 6-Hydroxychromone-3-carbaldehyde-3-hydroxybenzoylhydrazine with ctDNA. ACS Omega 2020, 5, 6928–6936. [Google Scholar] [CrossRef] [Green Version]
- Lerman, L.S. Structural considerations in the interaction of DNA and acridines. J. Mol. Biol. 1961, 3, 18–30. [Google Scholar] [CrossRef] [PubMed]
- Liu, G.D.; Liao, J.P.; Huang, S.S.; Shen, G.L.; Yu, R.Q. Fluorescence spectral study of interaction of water-soluble metal complexes of Schiff-base and DNA. Anal. Sci. 2001, 17, 1031–1036. [Google Scholar] [CrossRef] [Green Version]
- Goodwin, K.D.; Lewis, M.A.; Long, E.C.; Georgiadis, M.M. Crystal structure of DNA-bound Co(III) bleomycin B2: Insights on intercalation and minor groove binding. Proc. Natl. Acad. Sci. USA 2008, 105, 5052–5056. [Google Scholar] [CrossRef] [Green Version]
- Chen, Z.; Wu, Y.; Zhang, Q.; Zhang, Y. Biological properties of a benzothiazole-based mononuclear platinum(II) complex as a potential anticancer agent. J. Coord. Chem. 2020, 73, 1817–1832. [Google Scholar] [CrossRef]
- Racané, L.; Stojković, R.; Tralić-Kulenović, V.; Cerić, H.; Đaković, M.; Ester, K.; Mišir Krpan, A.; Radić Stojković, M. Interactions with polynucleotides and antitumor activity of amidino and imidazolinyl substituted 2-phenylbenzothiazole mesylates. Eur J. Med. Chem. 2014, 30, 4935. [Google Scholar] [CrossRef]
- Bradshaw, T.D.; Wrigley, S.; Shi, D.F.; Schultz, R.J.; Paull, K.D.; Stevens, M.F. 2-(4-Aminophenyl)benzothiazoles: Novel agents with selective profiles of in vitro anti-tumour activity. Br. J. Cancer 1998, 77, 745–752. [Google Scholar] [CrossRef] [PubMed]
- Bradshaw, T.D.; Stevens, M.F.; Westwell, A.D. The discovery of the potent and selective antitumour agent 2-(4-amino-3-methylphenyl)benzothiazole (DF 203) and related compounds. Curr. Med. Chem. 2001, 8, 203–210. [Google Scholar] [CrossRef] [PubMed]
- Shi, Y.; Cai, M.; Zhou, L.; Wang, H. The structure and function of cell membranes studied by atomic force microscopy. Semin. Cell Dev. Biol. 2018, 73, 31–44. [Google Scholar] [CrossRef] [PubMed]
- Kwon, J.H.; Park, H.J.; Chitrapriya, N.; Cho, T.S.; Kim, S.; Kim, J.; Hwang, I.H.; Kim, C.; Kim, S.K. DNA cleavage induced by [Cu(L)x(NO3)2] (L = 2,2′-dipyridylamine, 2,2′-bipyridine, dipicolylamine, x = 1 or 2): Effect of the ligand structure. J. Inorg. Biochem. 2014, 131, 79–86. [Google Scholar] [CrossRef] [PubMed]
- Romo, A.I.B.; Carepo, M.P.; Levin, P.; Nascimento, O.R.; Diaz, D.E.; Rodriguez-Lopez, J.; Leon, I.E.; Bezerra, L.F.; Lemus, L.; Diogenes, I.C.N. Synergy of DNA intercalation and catalytic activity of a copper complex towards improved polymerase inhibition and cancer cell cytotoxicity. Dalton Trans. 2021, 50, 11931–11940. [Google Scholar] [CrossRef]
- Husain, N.; Mahmood, R. Copper(II) generates ROS and RNS, impairs antioxidant system and damages membrane and DNA in human blood cells. Environ. Sci. Pollut. Res. Int. 2019, 26, 20654–20668. [Google Scholar] [CrossRef] [PubMed]
- Hricovini, M.; Mazur, M.; Sirbu, A.; Palamarciuc, O.; Arion, V.B.; Brezova, V. Copper(II) Thiosemicarbazone Complexes and Their Proligands upon UVA Irradiation: An EPR and Spectrophotometric Steady-State Study. Molecules 2018, 23, 721. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bolos, C.A.; Papazisis, K.T.; Kortsaris, A.H.; Voyatzi, S.; Zambouli, D.; Kyriakidis, D.A. Antiproliferative activity of mixed-ligand dien-Cu(II) complexes with thiazole, thiazoline and imidazole derivatives. J. Inorg. Biochem. 2002, 88, 25–36. [Google Scholar] [CrossRef]
- Leon, I.E.; Cadavid-Vargas, J.F.; Tiscornia, I.; Porro, V.; Castelli, S.; Katkar, P.; Desideri, A.; Bollati-Fogolin, M.; Etcheverry, S.B. Oxidovanadium(IV) complexes with chrysin and silibinin: Anticancer activity and mechanisms of action in a human colon adenocarcinoma model. J. Biol. Inorg. Chem. 2015, 20, 1175–1191. [Google Scholar] [CrossRef] [PubMed]
- Molinaro, C.; Wambang, N.; Bousquet, T.; Vercoutter-Edouart, A.S.; Pelinski, L.; Cailliau, K.; Martoriati, A. A Novel Copper(II) Indenoisoquinoline Complex Inhibits Topoisomerase I, Induces G2 Phase Arrest, and Autophagy in Three Adenocarcinomas. Front. Oncol. 2022, 12, 837373. [Google Scholar] [CrossRef]
- Bruker Analytical X-ray Systems. Apex2, User Manual, M86-E01078, 2nd ed.; Bruker Analytical X-ray Systems: Madison, WI, USA, 2006. [Google Scholar]
- Sheldrick, G.M. Siemens Industrial Automation. SADABS: Area-Detector Absorption Correction; Bruker AXS Inc.: Madison, WI, USA, 1996. [Google Scholar]
- Betteridge, P.W.C.; Carruthers, J.R.; Cooper, R.I.; Prout, K.; Watkin, D.J. Software for guided crystal structure analysis. J. Appl. Cryst. 2003, 36, 1487. [Google Scholar] [CrossRef]
- Palatinus, L.C.; Chapuis, G. SUPERFLIP—A Computer Program for the Solution of Crystal Structures by Charge Flipping in Arbitrary Dimensions. J. Appl. Crystallogr. 2007, 40, 786–790. [Google Scholar] [CrossRef] [Green Version]
- Watkin, D.J.; Prout, C.K.; Pearce, L.J. CAMERON; Chemical Crystallography Laboratory: Oxford, UK, 1996. [Google Scholar]
- McGhee, J.D.; von Hippel, P.H. Theoretical aspects of DNA-protein interactions: Co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. J. Mol. Biol. 1974, 86, 469–489. [Google Scholar] [CrossRef]
- Zeng, Z.F.; Huang, Q.P.; Cai, J.H.; Zheng, G.J.; Huang, Q.C.; Liu, Z.L.; Chen, Z.L.; Wei, Y.H. Synthesis, Characterization, DNA/HSA Interactions, and Anticancer Activity of Two Novel Copper(II) Complexes with 4-Chloro-3-Nitrobenzoic Acid Ligand. Molecules 2021, 26, 4028. [Google Scholar] [CrossRef] [PubMed]
- Devi, C.S.; Thulasiram, B.; Satyanarayana, S.; Nagababu, P. Analytical Techniques Used to Detect DNA Binding Modes of Ruthenium(II) Complexes with Extended Phenanthroline Ring. J. Fluoresc. 2017, 27, 2119–2130. [Google Scholar] [CrossRef] [PubMed]
- Mavroidi, B.; Kaminari, A.; Makrypidi, K.; Shegani, A.; Bouziotis, P.; Pirmettis, I.; Papadopoulos, M.; Sagnou, M.; Pelecanou, M. Biological evaluation of complexes of cyclopentadienyl M(CO)(3)(+) (M = Re, (99m)Tc) with high blood-brain barrier penetration potential as brain cancer agents. Investig. New Drugs 2022, 40, 497–505. [Google Scholar] [CrossRef]
- Halevas, E.; Mavroidi, B.; Antonoglou, O.; Hatzidimitriou, A.; Sagnou, M.; Pantazaki, A.A.; Litsardakis, G.; Pelecanou, M. Structurally characterized gallium-chrysin complexes with anticancer potential. Dalton Trans. 2020, 49, 2734–2746. [Google Scholar] [CrossRef] [PubMed]
Crystal Data | |
---|---|
Chemical formula sum | (C24H22CuN8O7S)n |
Chemical formula moiety | (C24H22CuN7O4S)n · n(NO3) |
Mr | n (630.10) |
Crystal system Space group | Monoclinic P21/n |
Temperature (K) | 295 |
a (Å) b (Å) c (Å) | 6.831 (5) 27.223 (14) 14.531 (9) |
β (°) | 102.309 (15) |
V (Å3) | 2640 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.97 |
Crystal size (mm) | 0.11 × 0.09 × 0.06 |
Data collection | |
Diffractometer | Bruker Kappa Apex2 |
Absorption correction | Numerical |
Tmin, Tmax | 0.92, 0.94 |
No. of reflections measured independent observed [I > 2.0σ(I)] | 23,579 5055 4225 |
Rint | 0.018 |
(sin θ/λ)max (Å−1) | 0.619 |
Refinement | |
R[F2 > 2σ(F2)] wR(F2) S | 0.040 0.057 1.00 |
No. of reflections | 4225 |
No. of parameters | 370 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.33–0.34 |
Bond Lengths (Å) | |
---|---|
Cu1—O3 i | 2.311 (2) |
Cu1—O1 | 2.0421 (18) |
Cu1—O2 | 2.494 (2) |
Cu1—N1 | 2.021 (2) |
Cu1—N2 | 1.966 (2) |
Cu1—N5 | 2.009 (2) |
Angles (°) | |
O3 i—Cu1—O1 | 93.32 (8) |
O3 i—Cu1—O2 | 168.08 (6) |
O1—Cu1—O2 | 77.26 (8) |
O3 i—Cu1—N1 | 103.05 (8) |
O1—Cu1—N1 | 160.14 (8) |
O2—Cu1—N1 | 87.70 (8) |
O3 i—Cu1—N2 | 93.53 (9) |
O1—Cu1—N2 | 84.22 (9) |
O2—Cu1—N2 | 92.77 (9) |
N1—Cu1—N2 | 83.62 (9) |
O3 i—Cu1—N5 | 84.75 (9) |
O1—Cu1—N5 | 92.37 (8) |
O2—Cu1—N5 | 88.32 (9) |
N1—Cu1—N5 | 100.17 (9) |
N2—Cu1—N5 | 176.10 (8) |
Cu1—O2—N7 | 159.60 (17) |
Cu1 ii—O3—N7 | 129.17 (16) |
IC50 (μΜ) | ||||||
---|---|---|---|---|---|---|
MCF-7 | MDA-MB-231 | U-87 MG | PC-3 | A-549 | DSF | |
Cu-1 | 2.2 ± 0.1 | 8.9 ± 1.5 | 25.2 ± 2.9 | 35.1 ± 2.4 | 39.7 ± 3.7 | 132.2 ± 6.7 |
L1 | 331.6 ± 5.9 | 398.2 ± 6.8 | 354.7 ± 7.9 | 405.2 ± 7.1 | 428.9 ± 8.8 | 736.2 ± 6.8 |
Cu(NO3)2·3H2O | 228.8 ± 6.1 | 292.1 ± 7.8 | 301.5 ± 8.1 | 299.8 ± 4.2 | 325.1 ± 4.9 | 367.7 ± 9.8 |
cisplatin | 7.0 ± 0.2 | 10.8 ± 0.9 | 5.6 ± 0.9 | 15.2 ± 2.1 | 8.9 ± 1.7 | 58.8 ± 7.9 |
G0/G1 | S | G2/M | |
---|---|---|---|
Cu-1 | 58.64 ± 3.01 | 6.52 ± 0.34 | 40.78 ± 1.01 |
L1 | 58.73 ± 3.29 | 16.91 ± 2.68 | 25.71 ± 1.09 |
control | 59.71 ± 3.23 | 16.24 ± 2.45 | 24.08 ± 3.51 |
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Mavroidi, B.; Sagnou, M.; Halevas, E.; Mitrikas, G.; Kapiris, F.; Bouziotis, P.; Hatzidimitriou, A.G.; Pelecanou, M.; Methenitis, C. A Tridentate Cu(II) Complex with a 2-(4′-Aminophenyl)Benzothiazole Derivative: Crystal Structure and Biological Evaluation for Anticancer Activity. Inorganics 2023, 11, 132. https://doi.org/10.3390/inorganics11030132
Mavroidi B, Sagnou M, Halevas E, Mitrikas G, Kapiris F, Bouziotis P, Hatzidimitriou AG, Pelecanou M, Methenitis C. A Tridentate Cu(II) Complex with a 2-(4′-Aminophenyl)Benzothiazole Derivative: Crystal Structure and Biological Evaluation for Anticancer Activity. Inorganics. 2023; 11(3):132. https://doi.org/10.3390/inorganics11030132
Chicago/Turabian StyleMavroidi, Barbara, Marina Sagnou, Eleftherios Halevas, George Mitrikas, Fotis Kapiris, Penelope Bouziotis, Antonios G. Hatzidimitriou, Maria Pelecanou, and Constantinos Methenitis. 2023. "A Tridentate Cu(II) Complex with a 2-(4′-Aminophenyl)Benzothiazole Derivative: Crystal Structure and Biological Evaluation for Anticancer Activity" Inorganics 11, no. 3: 132. https://doi.org/10.3390/inorganics11030132
APA StyleMavroidi, B., Sagnou, M., Halevas, E., Mitrikas, G., Kapiris, F., Bouziotis, P., Hatzidimitriou, A. G., Pelecanou, M., & Methenitis, C. (2023). A Tridentate Cu(II) Complex with a 2-(4′-Aminophenyl)Benzothiazole Derivative: Crystal Structure and Biological Evaluation for Anticancer Activity. Inorganics, 11(3), 132. https://doi.org/10.3390/inorganics11030132