Abstract
A cadmium(II) complex containing dppt ligand with the formula [CdCl2(dppt)2], where dppt is 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine was synthesized, elucidated and submitted to in vitro cytotoxicity studies against human breast (MCF-7), glioblastoma (U-87), and lung (A549) cancer cell lines as well as mouse embryo normal cell line (NIH/3T3), in comparison with cisplatin employing MTT assay over 24 and 48 h. The complex exhibited the highest cytotoxic effect against MCF-7 cells among the other three cell lines with IC50 values of 8.7 ± 0.5 (24 h) and 1.2 ± 0.7 µM (48 h). Significantly, flow cytometric assessment of the complex-treated MCF-7 and U-87 cells demonstrated a dose-dependent induced apoptotic cell death. The cellular morphological changes were in concord with cytotoxicity and flow cytometric results. The results of comet assay showed that the complex is able to induce DNA damage in MCF-7 cells. These observations are of importance, as sustained damage to cellular DNA could lead to apoptotic cell death. The results of DNA-binding studies indicated that the complex fits into the DNA minor groove and interacts with DNA via a partial intercalation. Moreover, the complex was able to efficiently cleave pUC19 DNA through a hydrolytic mechanism. The binding affinity between the complex and apoptosis-relevant protein targets including APAF1, Bax, Bcl-2, Cas3, Cas7, and Cas9 was evaluated through molecular docking studies. In silico virtual studies revealed the complex’s strong affinity towards apoptosis-related proteins; therefore the complex can act as a potential apoptosis inducer. Physicochemical, pharmacokinetics, lipophilicity, drug-likeness, and medicinal chemistry properties of the complex were also predicted through in silico absorption, distribution, metabolism and excretion studies.
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Abyar S, Khandar AA, Salehi R, Hosseini-Yazdi SA, Alizadeh E, Mahkam M, Jamalpoor A, White JM, Shojaei M, Aizpurua-Olaizola O, Masereeuw R, Janssen MJ (2019) In vitro nephrotoxicity and anticancer potency of newly synthesized cadmium complexes. Sci Rep 9:14686. https://doi.org/10.1038/s41598-019-51109-9
Ahamed M, Akhtar MJ, Khan MAM, Alhadlaq HA (2020) Reduced graphene oxide mitigates cadmium-induced cytotoxicity and oxidative stress in HepG2 cells. Food Chem Toxicol 143:111515. https://doi.org/10.1016/j.fct.2020.111515
Ajibade PA, Fatokun AA, Andrew FP (2020) Synthesis, characterization and anti-cancer studies of Mn(II), Cu(II), Zn(II) and Pt(II) dithiocarbamate complexes - crystal structures of the Cu(II) and Pt (II) complexes. Inorg Chim Acta 504:119431. https://doi.org/10.1016/j.ica.2020.119431
Alalawy MD, Patel UH, Bhatt BS, Patel NJ (2020) Exploring qualitative and quantitative contributions of intermolecular interactions, DNA-binding and in vitro cytotoxic activity of isostructural and isomorphous Cd and Zn complexes. Polyhedron 185:114595. https://doi.org/10.1016/j.poly.2020.114595
Aljahdali MS, El-Sherif AA (2020) Synthesis and biological evaluation of novel Zn(II) and Cd(II) Schiff base complexes as antimicrobial, antifungal, and antioxidant agents. Bioinorg Chem Appl 2020:1–17. https://doi.org/10.1155/2020/8866382
Anighoro A, Bajorath J, Rastelli G (2014) Polypharmacology: challenges and opportunities in drug discovery. J Med Chem 57:7874–7887. https://doi.org/10.1021/jm5006463
Anjomshoa M, Fatemi SJ, Torkzadeh-Mahani M, Hadadzadeh H (2014) DNA-and BSA-binding studies and anticancer activity against human breast cancer cells (MCF-7) of the zinc(II) complex coordinated by 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine. Spectrochim Acta Part A Mol Biomol Spectrosc 127:511–520. https://doi.org/10.1016/j.saa.2014.02.048
Anjomshoa M, Hadadzadeh H, Fatemi SJ, Torkzadeh-Mahani M (2015a) A mononuclear Ni (II) complex with 5, 6-diphenyl-3-(2-pyridyl)-1, 2, 4-triazine: DNA- and BSA-binding and anticancer activity against human breast carcinoma cells. Spectrochim Acta Part A Mol Biomol Spectrosc 136:205–215. https://doi.org/10.1016/j.saa.2014.09.016
Anjomshoa M, Hadadzadeh H, Torkzadeh-Mahani M, Fatemi SJ, Adeli-Sardou M, Rudbari HA, Nardo VM (2015b) A mononuclear Cu(II) complex with 5, 6-diphenyl-3-(2-pyridyl)-1,2,4-triazine: synthesis, crystal structure, DNA-and BSA-binding, molecular modeling, and anticancer activity against MCF-7, A-549, and HT-29 cell lines. Eur J Med Chem 96:66–82. https://doi.org/10.1016/j.ejmech.2015.04.020
Anjomshoa M, Torkzadeh-Mahani M, Sahihi M, Rizzoli C, Ansari M, Janczak J, Sherafat Esfahani S, Ataei F, Dehkhodaei M, Amirheidari B (2019) Tris-chelated complexes of nickel(II) with bipyridine derivatives: DNA binding and cleavage, BSA binding, molecular docking, and cytotoxicity. J Biomol Struct Dyn 37:3887–3904. https://doi.org/10.1080/07391102.2018.1534700
Anjomshoa M, Amirheidari B (2022) Nuclease-like metalloscissors: biomimetic candidates for cancer and bacterial and viral infections therapy. Coord Chem Rev 458:214417. https://doi.org/10.1016/j.ccr.2022.214417
Arshad M, Bhat AR, Hoi KK, Choi I, Athar F (2017) Synthesis, characterization and antibacterial screening of some novel 1,2,4-triazine derivatives. Chin Chem Lett 28:1559–1565. https://doi.org/10.1016/j.cclet.2016.12.037
Babgi BA, Mashat KH, Abdellattif MH, Arshad MN, Alzahrani KA, Asiri AM, Du J, Humphrey MG, Hussien MA (2020) Synthesis, structures, DNA-binding, cytotoxicity and molecular docking of CuBr (PPh3)(diimine). Polyhedron 192:114847. https://doi.org/10.1016/j.poly.2020.114847
Bhaskaran M, Devegowda VG, Gupta VK, Shivachar A, Bhosale RR, Arunachalam M, Vaishnavi T (2020) Current perspectives on therapies, including drug delivery systems, for managing glioblastoma multiforme. ACS Chem Neurosci 11:2962–2977. https://doi.org/10.1021/acschemneuro.0c00555
Bhattacharyya MK, Dutta D, Nashre-ul-Islam SM, Frontera A, Sharma P, Verma AK, Das A (2020) Energetically significant antiparallel π-stacking contacts in Co(II), Ni(II) and Cu(II) coordination compounds of pyridine-2,6-dicarboxylates: antiproliferative evaluation and theoretical studies. Inorg Chim Acta 501:119233. https://doi.org/10.1016/j.ica.2019.119233
Bojarska J, Remko M, Breza M, Madura ID, Kaczmarek K, Zabrocki J, Wolf WM (2020) A supramolecular approach to structure-based design with a focus on synthons hierarchy in ornithine-derived ligands: review, synthesis, experimental and in silico studies. Molecules 25:1135. https://doi.org/10.3390/molecules25051135
Bravo C, Robalo MP, Marques F, Fernandes AR, Sequeira DA, Piedade MFM, Garcia MH, de Brito MJV, Morais TS (2019) First heterobimetallic Cu(I)–dppf complexes designed for anticancer applications: synthesis, structural characterization and cytotoxicity. New J Chem 43:12308–12317. https://doi.org/10.1039/c9nj02068c
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
Cascioferro S, Parrino B, Spanò V, Carbone A, Montalbano A, Barraja P, Diana P, Cirrincione G (2017) An overview on the recent developments of 1,2,4-triazine derivatives as anticancer compounds. Eur J Med Chem 142:328–375. https://doi.org/10.1016/j.ejmech.2017.08.009
Chen Z, Wu Y, Zhu Z, Zhang Y (2019) DNA cleavage, DNA/HSA binding study, and antiproliferative activity of a phenolate-bridged binuclear copper(II) complex. Biometals 32:227–240. https://doi.org/10.1007/s10534-019-00172-w
Daina A, Zoete V (2016) A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 11:1117–1121. https://doi.org/10.1002/cmdc.201600182
Daina A, Blatter MC, Gerritsen VB, Palagi PM, Marek D, Xenarios I, Schwede T, Michielin O, Zoete V (2017a) Drug design workshop: a web-based educational tool to introduce computer-aided drug design to the general public. J Chem Educ 94:335–344. https://doi.org/10.1021/acs.jchemed.6b00596
Daina A, Michielin O, Zoete V (2017b) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:1–13. https://doi.org/10.1038/srep42717
Desbouis D, Troitsky IP, Belousoff MJ, Spiccia L, Graham B (2012) Copper(II), zinc(II) and nickel(II) complexes as nuclease mimetics. Coord Chem Rev 256:897–937. https://doi.org/10.1016/j.ccr.2011.12.005
Dutta D, Sharma P, Frontera A, Gogoi A, Verma AK, Dutta D, Sarma B, Bhattacharyya MK (2020) Oxalato bridged coordination polymer of manganese(III) involving unconventional O∙∙∙π-hole(nitrile) and antiparallel nitrile∙∙∙nitrile contacts: antiproliferative evaluation and theoretical studies. New J Chem 44:20021–20038. https://doi.org/10.1039/D0NJ03712E
Fang Y, Li J, Han PP, Han QX, Li MX (2018) Less toxic zinc (II), diorganotin (IV), gallium (III) and cadmium (II) complexes derived from 2-benzoylpyridine N,N-dimethylthiosemicarbazone: synthesis, crystal structures, cytotoxicity and investigations of mechanisms of action. Toxicol Res 7:987–993. https://doi.org/10.1039/c8tx00127h
Fathima SSA, Paulpandiyan R, Nagarajana ER (2018) Expatiating biological excellence of aminoantipyrine derived novel metal complexes: combined DNA interaction, antimicrobial, free radical scavenging studies and molecular docking simulations. J Mol Struct 1178:179–191. https://doi.org/10.1016/j.molstruc.2018.10.021
Gitarić J, Stanojević IM, Rodić MV, Drašković NS, Stevanović M, Vojnović S, Djuran MI, Glišić BĐ (2020) Structural characterization and biological evaluation of polynuclear Mn(II) and Cd(II) complexes with 2, 2-dimethyl-1, 3-propanediamine-N, N, N’, N’-tetraacetate The influence of ligand structure and counter cation on the complex nuclearity. Polyhedron 188:114688. https://doi.org/10.1016/j.poly.2020.114688
Gogoi A, Das A, Frontera A, Verma AK, Bhattacharyya MK (2019) Energetically significant unconventional π-π contacts involving fumarate in a novel coordination polymer of Zn(II): In-vitro anticancer evaluation and theoretical studies. Inorg Chim Acta 493:1–13. https://doi.org/10.1016/j.ica.2019.04.047
Guan QL, Liu Z, Wei WJ, Xing YH, Liu J, Zhang R, Hou YN, Wang X, Bai FY (2014) Synthesis, structure, spectroscopy of four novel supramolecular complexes and cytotoxicity study by application of multiple parallel perfused microbioreactors. New J Chem 38:3258–3268. https://doi.org/10.1039/c3nj01646c
Ibrahim AO, Zhou Y, Jiang F, Chen L, Li X, Xu W, Onawumi OO, Odunola OA, Hong M (2011) An unusual (10,3)-d MOF material with nanoscale helical cavities and multifunctionality. Eur J Inorg Chem 2011:5000–5005. https://doi.org/10.1002/ejic.201100566
Jeyalakshmi K, Haribabu J, Balachandran C, Bhuvanesh NSP, Emi N, Karvembu R (2017) Synthesis of Ru(II)–benzene complexes containing aroylthiourea ligands, and their binding with biomolecules and in vitro cytotoxicity through apoptosis. New J Chem 41:2672–2686. https://doi.org/10.1039/c6nj03099h
Jin Y, Cowan JA (2005) DNA cleavage by copper-ATCUN complexes. Factors influencing cleavage mechanism and linearization of dsDNA. J Am Chem Soc 127:8408–8415. https://doi.org/10.1021/ja0503985.s001
Khan T, Ahmad R, Azad I, Raza S, Joshi S, Khan AR (2018) Computer-aided drug design and virtual screening of targeted combinatorial libraries of mixed-ligand transition metal complexes of 2-butanone thiosemicarbazon. Comput Biol Chem 75:178–195. https://doi.org/10.1016/j.compbiolchem.2018.05.008
Khandar AA, Azar ZM, Eskandani M, Hubschle CB, van Smaalen S, Shaabani B, Omidi Y (2019) Cadmium(II) complexes of a hydrazone ligand: synthesis, characterization, DNA binding, cyto-and genotoxicity studies. Polyhedron 171:237–248. https://doi.org/10.1016/j.poly.2019.06.026
Korkmaz N, Karadağ A, Aydın A, Yanar Y, Karaman İ, Tekin Ş (2014) Synthesis and characterization of two novel dicyanidoargentate(I) complexes containing N-(2-hydroxyethyl) ethylenediamine exhibiting significant biological activity. New J Chem 38:4760–4773. https://doi.org/10.1039/c4nj00851k
L’Azou B, Passagne I, Mounicou S, Tréguer-Delapierre M, Puljalté I, Szpunar J, Lobinski R, Ohayon-Courtѐs C (2014) Comparative cytotoxicity of cadmium forms (CdCl2, CdO, CdS micro-and nanoparticles) in renal cells. Toxicol Res 3:32–41. https://doi.org/10.1039/c3tx50063b
Li J, Huang WY, Qian SS, Li QY, Zhu HL (2015a) Two novel 2D waves copper(II) coordination polymer with the quinolone antimicrobial drugs ciprofloxacin: synthesis, structure and biological evaluation. Inorg Chim Acta 435:16–24. https://doi.org/10.1016/j.ica.2015.06.001
Li F, Xie J, Feng F (2015b) Copper and zinc complexes of a diaza-crown ether as artificial nucleases for the efficient hydrolytic cleavage of DNA. New J Chem 39:5654–5660. https://doi.org/10.1039/c4nj02193b
Li J, Liu R, Jiang J, Liang X, Huang G, Yang D, Chen H, Pan L, Ma Z (2020) Synthesis, characterization, photoluminescence, antiproliferative activity, and DNA interaction of cadmium(II) substituted 4′-phenyl-terpyridine compounds. J Inorg Biochem 210:111165. https://doi.org/10.1016/j.jinorgbio.2020.111165
Liu P, Liu J, Zhang YQ, Wu BY, Wang KZ (2015) Synthesis, DNA binding and photocleavage, and cellular uptake of an alkyl chain-linked dinuclear ruthenium (II) complex. J Photochem Photobiol B Biol 143:89–99. https://doi.org/10.1016/j.jphotobiol.2015.01.004
Lopes J, Alves D, Morais TS, Costa PJ, Piedade MFM, Marques F, de Brito MJV, Garcia MH (2017) New copper(I) and heteronuclear copper(I)–ruthenium(II) complexes: synthesis, structural characterization and cytotoxicity. J Inorg Biochem 169:68–78. https://doi.org/10.1016/j.jinorgbio.2017.01.007
Lopes ED, Oliveira CG, Silva PB, Eismann CE, Suárez CA, Menegário AA, Leite CQF, Deflon VM, Pavan FR (2016) Novel zinc(II) complexes [Zn(atc-Et)2] and [Zn(atc-Ph)2]: in vitro and in vivo antiproliferative studies. Int J Mol Sci 17:781. https://doi.org/10.3390/ijms17050781
Luo HY, Li JY, Li Y, Zhang L, Li JY, Jia DZ, Xu GC (2016) Cadmium(II) complexes with a 4-acyl pyrazolone derivative and co-ligands: crystal structures and antitumor activity. RSC Adv 6:114997–115009. https://doi.org/10.1039/c6ra23938b
Ma Y, Rivera-Ingraham G, Nommick A, Bickmeyer U, Roeder T (2020) Copper and cadmium administration induce toxicity and oxidative stress in the marine flatworm Macrostomum lignano. Aquat Toxicol 221:105428. https://doi.org/10.1016/j.aquatox.2020.105428
Machura B, Świtlicka A, Kruszynski R, Mroziński J, Kłak J, Kusz J (2008) Coordination studies of 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine towards Cu2+ cation. X-ray studies, spectroscopic characterization and DFT calculations. Polyhedron 27:2959–2967. https://doi.org/10.1016/j.poly.2008.05.033
Majumdar D, Biswas JK, Mondal M, Babu MSS, Das S, Metre RK, SreeKumar SS, Bankura K, Mishra D (2018) Cd(II) pseudohalide complexes with N, N′-bis (3-ethoxysalicylidenimino) 1, 3-diaminopropane: crystal structures, hirshfeld surface, antibacterial and anti-biofilm properties. ChemistrySelect 3:2912–2925. https://doi.org/10.1002/slct.201702970
Manikandan R, Chitrapriya N, Jang YJ, Viswanathamurthi P (2013) Evaluation of DNA-binding, radical scavenging and cytotoxic activity of five coordinated Cd(II) complexes containing 2-acetylpyridine-N 4-substituted thiosemicarbazone. RSC Adv 3:11647–11657. https://doi.org/10.1039/c3ra40814k
Marandi F, Fun HK, Quah CK (2011) Synthesis of new complexes of cadmium(II) with 3-(2-Pyridyl)-5, 6-diphenyl-1,2,4-triazine ligand: study of the effect of weak interactions on their crystal packing. Synth React Inorg M 41:234–240. https://doi.org/10.1080/15533174.2011.555852
Martínez MÁ, Carranza MP, Massaguer A, Santos L, Organero JA, Aliende C, de Llorens R, Ng-Choi I, Feliu L, Planas M, Rodríguez AM, Manzano BR, Espino G, Jalón FA (2017) Synthesis and biological evaluation of Ru(II) and Pt(II) complexes bearing carboxyl groups as potential anticancer targeted drugs. Inorg Chem 56:13679–13696. https://doi.org/10.1021/acs.inorgchem.7b01178
Matos CP, Adiguzel Z, Yildizhan Y, Cevatemre B, Onder TB, Cevik O, Nunes P, Ferreira LP, Carvalho MD, Campos DL, Pavan FR, Pessoa JC, Garcia MH, Tomaz AI, Correia I, Acilan C (2019) May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents? Eur J Med Chem 176:492–512. https://doi.org/10.1016/j.ejmech.2019.04.070
Mishra A, Dey S (2019) Molecular docking studies of a cyclic octapeptide-cyclosaplin from sandalwood. Biomolecules 9:740. https://doi.org/10.3390/biom9110740
Mlejnek P, Dolezel P, Maier V, Kikalova K, Skoupa N (2019) N-acetylcysteine dual and antagonistic effect on cadmium cytotoxicity in human leukemia cells. Environ Toxicol Pharmacol 71:103213. https://doi.org/10.1016/j.etap.2019.103213
Morgan SM, El-Sonbati AZ, Eissa HR (2017) Geometrical structures, thermal properties and spectroscopic studies of Schiff base complexes: correlation between ionic radius of metal complexes and DNA binding. J Mol Liq 240:752–776. https://doi.org/10.1016/j.molliq.2017.05.114
Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662. https://doi.org/10.1002/(sici)1096-987x(19981115)19:14%3c1639::aid-jcc10%3e3.0.co;2-b
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4
Nath H, Dutta D, Sharma P, Frontera A, Verma AK, Barceló-Oliver M, Devi M, Bhattacharyya MK (2020) Adipato bridged novel hexanuclear Cu(II) and polymeric Co(II) coordination compounds involving cooperative supramolecular assemblies and encapsulated guest water clusters in square grid host: antiproliferative evaluation and theoretical studies. Dalton Trans 49:9863–9881. https://doi.org/10.1039/D0DT01007C
Nath H, Sharma P, Gomila RM, Frontera A, Barceló-Oliver M, Verma AK, Dutta K, Bhattacharyya MK (2021) Unconventional enclathration of guest adipic acid and energetically significant antiparallel π-stacked ternary assemblies involving unusual regium- π(chelate) contacts in phenanthroline-based Ni(II) and Cu(II) compounds—antiproliferative evaluation and theoretical studies. J Mol Struct 1245:131038. https://doi.org/10.1016/j.molstruc.2021.131038
Qazi SU, Rahman SU, Awan AN, al-Rashida M, Alharthy RD, Asari A, Hameed A, Iqbal J (2018) Semicarbazone derivatives as urease inhibitors: synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation. Bioorg Chem 79:19–26. https://doi.org/10.1016/j.bioorg.2018.03.02
Rukk NS, Kuzmina LG, Shamsiev RS, Davydova GA, Mironova EA, Ermakov AM, Buzanov GA, Skryabina AY, Streletskii AN, Vorob’eva GA, Retivov VM, Volkov PA, Belus SK, Kozhukhova EI, Krasnoperova VN (2019) Zinc (II) and cadmium (II) halide complexes with caffeine: synthesis, X-ray crystal structure, cytotoxicity and genotoxicity studies. Inorg Chim Acta 487:184–200. https://doi.org/10.1016/j.ica.2018.11.036
Sharma P, Dutta D, Gomila RM, Frontera A, Barcelo-Oliver M, Verma AK, Bhattacharyya MK (2021) Benzoato bridged dinuclear Mn(II) and Cu(II) compounds involving guest chlorobenzoates and dimeric paddle wheel supramolecular assemblies: antiproliferative evaluation and theoretical studies. Polyhedron 208:115409. https://doi.org/10.1016/j.poly.2021.115409
Spel L, Boelens JJ, Nierkens S, Boes M (2013) Antitumor immune responses mediated by dendritic cells: how signals derived from dying cancer cells drive antigen cross-presentation. OncoImmunology 2:e26403. https://doi.org/10.4161/onci.26403
Tsave O, Iordanidou C, Gabriel C, Hatzidimitriou A, Salifoglou A (2019) Binary-ternary Cd (II)-(hydroxycarboxylic acid)-(aromatic chelator) systems exhibit in vitro cytotoxic selectivity in a tissue-specific manner. J Inorg Biochem 195:201–215. https://doi.org/10.1016/j.jinorgbio.2019.02.009
Wang B, Wang H, Han D, Chen J, Yin Y (2020) Studying the mixture effects of brominated flame retardants and metal ions by comet assay. Environ Pollut 267:115677. https://doi.org/10.1016/j.envpol.2020.115677
Yamada A, Mabe T, Yamane R, Noda K, Wasada Y, Inamo M, Ishihara K, Suzuki T, Takagi HD (2015) Flipping of the coordinated triazine moiety in Cu(I)–L2 and the small electronic factor, κel, for direct outer-sphere cross reactions: syntheses, crystal structures and redox behaviour of copper (II)/(I)–L2 complexes (L= 3-(2-pyridyl)-5, 6-diphenyl-1, 2, 4-triazine). Dalton Trans 44:13979–13990. https://doi.org/10.1039/c5dt01808k
Zhang N, Fan Y, Huang G, Buac D, Bi C, Ma Y, Wang X, Zhang Z, Zhang X, Dou QP (2017) l-tryptophan Schiff base cadmium(II) complexes as a new class of proteasome inhibitors and apoptosis inducers in human breast cancer cells. Inorg Chim Acta 466:478–485. https://doi.org/10.1016/j.ica.2017.07.006
Zhang HB, Zhang XF, Chai LQ, Tang LJ, Zhang HS (2020) Zinc(II) and cadmium(II) complexes containing imidazole ring: structural, spectroscopic, antibacterial, DFT calculations and Hirshfeld surface analysis. Inorg Chim Acta 507:119610. https://doi.org/10.1016/j.ica.2020.119610
Zhao J, Peng K, Guo Y, Zhang J, Chen S, Hu J (2015) Photoluminescent and cytotoxic properties of multinuclear complexes and multinuclear-based polymers with group 12 metals and tripodal ligand. New J Chem 39:6016–6024. https://doi.org/10.1039/C5NJ00222B
Zvirzdinaite M, Garbe S, Arefyeva N, Krause M, von der Stück R, Klein A (2017) Palladium(II) complexes of ambidentate and potentially cyclometalating 5-aryl-3-(2′-pyridyl)-1,2,4-triazine ligands. Eur J Inorg Chem 2017:2011–2022. https://doi.org/10.1002/ejic.201601530
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The authors would like to thank the Faculty of Pharmacy and Pharmaceutics Research Center, Kerman University of Medical Sciences, Kerman, Iran for their support. This study was approved by Kerman University of Medical Sciences with the research proposal number 400000640.
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MA: Carrying out the experiments and writing the manuscript. MS: Carrying out the molecular docking studies. SJF: Synthesis data curation. SS: Carrying out MTT assay. AF: Flow cytometry data curation. BA: ADME studies, data curation, editing the manuscript, and supervising the whole work.
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Anjomshoa, M., Sahihi, M., Fatemi, S.J. et al. In vitro biological and in silico molecular docking and ADME studies of a substituted triazine-coordinated cadmium(II) ion: efficient cytotoxicity, apoptosis, genotoxicity, and nuclease-like activity plus binding affinity towards apoptosis-related proteins. Biometals 35, 549–572 (2022). https://doi.org/10.1007/s10534-022-00387-4
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DOI: https://doi.org/10.1007/s10534-022-00387-4