Abstract
The structure of complex cis-Pd(HLMe)Cl2 was studied both in solution and in solid state using multinuclear (1H, 13C, 15N) NMR spectroscopy and X-ray structural analysis. Complex was evaluated for cytotoxic activity. Thus, the results showed that cis-Pd(HLMe)Cl2 has a pronounced cytotoxicity toward human leukemic lymphoblast’s CCRF-CEM and cervix adenocarcinoma HeLa cells. Moreover, it was found that cis-Pd(HLMe)Cl2 is more toxic than cisplatin: its IC50 value at 24 h incubation was lower by more than an order for CCRF-CEM cells and by three orders for HeLa cells as compared with cisplatin IC50. Depending on the concentration, cis-Pd(HLMe)Cl2 is accelerated or slowed hemolysis of erythrocytes. Observed differential biological effects of cis-Pd(HLMe)Cl2 suggest the dependence of the agent’s interactions with cells on the molecular structure of palladium ligand and the cell type.
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References
Allardyce CS, Dyson PJ (2016) Metal-based drugs that break the rules. Dalton Trans 45(8):3201–3209. https://doi.org/10.1039/c5dt03919c
Al-Masoudi NA, Abdullah BH, Essa AH, Loddo R, LaColla P (2010) Platinum and palladium-triazole complexes as highly potential antitumor agents. Arch Pharm Pharm Med Chem 343:222–227. https://doi.org/10.1002/ardp.200900140
Brookhart M, Greenb ML, Parkin G (2007) Agostic interactions in transition metal compounds. PNAS 104(17):6908–6914. https://doi.org/10.1073/pnas.0610747104
Bruijnincx PCA, Sadler PJ (2008) New trends for metal complexes with anticancer activity. Curr Opin Chem Biol 12(2):197–206. https://doi.org/10.1016/j.cbpa.2007.11.013
Caires A, Carlos F (2007) Recent advances involving palladium(II) complexes for the cancer therapy. Anticancer Agents Med Chem 7(5):484–491. https://doi.org/10.2174/187152007781668661
Canty AJ, Skelton BW, Traill PR, White AH (1992) Structural chemistry of the platinum group-metals: MCl2(bpy) (M = Pd, Pt, bpy = 2,2′-bipyridine. Aust J Chem 45:417. https://doi.org/10.1071/CH9920417
Carmichael J, Degraff WG, Gazdar AF, Minna JD, Mitchell JB (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 47:936–942
Chi Y, Tong B, Chou P-T (2014a) Metal complexes with pyridyl azolates: design, preparation and applications. Coord Chem Rev 281:1–25. https://doi.org/10.1016/j.ccr.2014.08.012
Chi Z, Liu R, You H, Ma S, Cui H (2014b) Probing the in vitro cytotoxicity of the veterinary drug oxytetracycline. PLoS ONE 9(7):e102334. https://doi.org/10.1371/journal.pone.0102334
CrysAlisPro Software system, version 1.171.40_64.67 (2015) Rigaku Corporation, Oxford
Cueva-Alique I, Muñoz-Moreno L, Torre-Rubio E, Bajo AM, Gude L, Cuenca T, Royo E (2019) Water soluble, optically active monofunctional Pd(II) and Pt(II) compounds: promising adhesive and antimigratory effects on human prostate PC-3 cancer cells. Dalton Trans 48:14279–14293. https://doi.org/10.1039/C9DT02873K
Deepthi SB, Trivedi R, Sujitha P, Kumar CG, Sridhar B, Bhargava S (2012) Synthesis, characterization and cytotoxic activity of palladium(II) carbohydrate complexes. J Chem Sci 124(6):1405–1413
Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JAK, Puschmann H (2009) OLEX2: a complete structure solution, refinement and analysis program. J Appl Crystallogr 42:339–341. https://doi.org/10.1107/S0021889808042726
Fanelli M, Formica M, Fusi V, Giorgi L, Micheloni M, Paoli P (2016) New trends in platinum and palladium complexes as antineoplastic agents. Coord Chem Rev 310:41–79. https://doi.org/10.1016/j.ccr.2015.11.004
Filimonov DA, Druzhilovskiy DS, Lagunin AA, Gloriozova TA, Rudik AV, Dmitriev AV, Pogodin PV, Poroikov VV (2018) Computer-aided prediction of biological activity spectra for chemical compounds: opportunities and limitations. Biomed Chem Res Methods 1(1):1–21. https://doi.org/10.18097/bmcrm00004
Florea AM, Büsselberg D (2011) Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 3:1351–1371. https://doi.org/10.3390/cancers3011351
Garbutcheon-Singh KB, Grant MP, Harper BW, Krause-Heuer AM, Manohar M, Orkey N, Aldrich-Wright JR (2011) Transition metal based anticancer drugs. Curr Top Med Chem 11(5):521–542. https://doi.org/10.2174/156802611794785226
Harper BW, Krause-Heuer AM, Grant MP, Manohar M, Garbutcheon-Singh KB, Aldrich-Wright JR (2010) Advances in platinum chemotherapeutics. Chem Eur J 16:7064–7077. https://doi.org/10.1002/chem.201000148
Hartinger CG, Dyson PJ (2009) Bioorganometallic chemistry—from teaching paradigms to medicinal applications. Chem Soc Rev 38(2):391–401. https://doi.org/10.1039/b707077m
Huang H, Zhu L, Reid BR, Drobny GP, Hopkins PB (1995) Solution structure of a cisplatin-induced DNA interstand cross link. Science 270:1842–1845. https://doi.org/10.1126/science.270.5243.1842
Jahromi EZ, Divsalar A, Saboury AA, Khaleghizadeh S, Mansouri-Torshizi H, Kostova I (2016) Palladium complexes: new candidates for anti-cancer drugs. J Iran Chem Soc 13:967–989. https://doi.org/10.1007/s13738-015-0804-8
Kapdi AR, Fairlamb IJ (2014) Anti-cancer palladium complexes: a focus on PdX2L2, palladacycles and related complexes. Chem Soc Rev 43(13):4751–4777. https://doi.org/10.1039/c4cs00063c
Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7:573–584. https://doi.org/10.1038/nrc2167
Khomenko DM, Doroschuk RO, Lampeka RD (2015) Synthesis, characterization and luminescent properties of palladium complexes with 3-(2-pyridyl)-1H-1,2,4-triazole-5-acetic acid ethyl ester. Polyhedron 100:82–88. https://doi.org/10.1016/j.poly.2015.06.036
Kozachkova OM, Tsaryk NV, Trachevskyi VV, Rozhenko AB, Shermolovich YuH, Guzyr OI, Sharykina NI, Chekhun VF, Pekhnyo VI (2017) Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphonic acid and their antitumor activity. Ukr Biochem J 89(2):106–115. https://doi.org/10.15407/ubj89.02.106
Kroutil O, Prědota M, Chval Z (2016) Pt⋯H nonclassical interaction in water-dissolved Pt(II) complexes: coaction of electronic effects with solvent-assisted stabilization. Inorg Chem 55(7):3252–3264. https://doi.org/10.1021/acs.inorgchem.5b02261
Kutschy P, Sýkora A, Čurillová Z, Repovská M, Pilátová M, Mojžiš J, Mezencev R, Pazdera P, Hromjáková T (2010) Glyoxyl analogs of indole phytoalexins: synthesis and anticancer activity. Collect Czech Chem Commun 75(8):887–903. https://doi.org/10.1135/cccc2010048
Lagunin A, Stepanchikova A, Filimonov D, Poroikov V (2000) PASS: prediction of activity spectra for biologically active substances. Bioinformatics 16(8):747–748. https://doi.org/10.1093/bioinformatics/16.8.747
Lazarevic T, Rilak A, Bugarcic ZD (2017) Platinum, palladium, gold and ruthenium complexes as anticancer agents: current clinical uses, cytotoxicity studies and future perspectives. Eur J Med Chem 142:8–31. https://doi.org/10.1016/j.ejmech.2017.04.007
Liu W, Gust R (2016) Update on metal N-heterocyclic carbene complexes as potential anti-tumor metallodrugs. Coord Chem Rev 329:191–213. https://doi.org/10.1016/j.ccr.2016.09.004
Maškovi J, Hatzidimitriou A, Damjanovic A, Stanojkovic T, Trifunovic SR, Geronikaki A, Papagiannopoulou D (2018) Synthesis, characterization and biological evaluation of Pd(II), Cu(II), Re(I) and 99mTc(I) thiazole-based complexes. Med Chem Commun 9:831–842. https://doi.org/10.1039/C8MD00067K
Misirlic-Dencic S, Poljarevic J, Isakovic AM, Sabo T, Markovic I, Trajkovic V (2020) Current development of metal complexes with diamine ligands as potential anticancer agents. Curr Med Chem 27(3):380–410. https://doi.org/10.2174/0929867325666181031114306
Natile G, Marzilli LG (2006) Non-covalent interactions in adducts of platinum drugs with nucleobases innucleotides and DNA as revealed by using chiral substrates. Coord Chem Rev 250:1315–1331. https://doi.org/10.1016/j.ccr.2005.12.004
Ndagi U, Mhlongo N, Soliman ME (2017) Metal complexes in cancer therapy—an update from drug design perspective. Drug Des Devel Ther 11:599–616. https://doi.org/10.2147/DDDT.S119488
Potts KT (1961) The chemistry of 1,2,4-triazoles. Chem Rev 61(2):87–127. https://doi.org/10.1021/cr60210a001
Şahin Ö, Özdemir ÜÖ, Seferoğlu N, Genc ZK, Kaya K, Aydıner B, Tekin S, Seferoğlu Z (2018) New platinum(II) and palladium(II) complexes of coumarin–thiazole Schiff base with a fluorescent chemosensor properties: Synthesis, spectroscopic characterization, X-ray structure determination, in vitro anticancer activity on various human carcinoma cell lines and computational studies. J Photochem Photobiol B Biol. https://doi.org/10.1016/j.jphotobiol.2017.11.030
Sheldrick GM (2015a) Integrated space-group and crystal-structure determination. Acta Crystallogr A 71:3–8. https://doi.org/10.1107/S2053273314026370
Sheldrick GM (2015b) Crystal structure refinement with SHELXL. Acta Crystallogr C 71:3–8. https://doi.org/10.1107/S2053229614024218
Terskov IA, Gitelzon II (1957) Method of chemical (acid) erythrograms. Biophysics 2(2):259–266
Teyssot M-L, Jarrousse A-S, Manin M, Chevry A, Roche S, Norre F, Beaudoin C, Morel L, Boyer D, Mahiou R, Gautier A (2009) Metal-NHC complexes: a survey of anti-cancer properties. Dalton Trans 35:6894–6902. https://doi.org/10.1039/b906308k
Thakur A, Gupta PS, Shukla PK, Verma A, Pathak P (2016) 1,2,4-Triazole scafolds: recent advances and pharmacological applications. Int J Curr Res Acad Rev 4(2):277–296. https://doi.org/10.20546/ijcrar.2016.402.031
Veljković DŽ, Đunović AB, Zarić SD (2019) Significant differences in the energy of X–H/Pt interactions between cisplatin and transplatin molecules. ChemistrySelect 4:12909–12914. https://doi.org/10.1002/slct.201903296
Zakharchenko BV, Khomenko DM, Doroshchuk RO, Raspertova IV, Severynovska OV, Starova VS, Lampeka RD (2017) Influence of nature of the substituent in the 3-(2-pyridyl)-1,2,4-triazole for complexation with Pd2+. Chem Pap 71:2003. https://doi.org/10.1007/s11696-017-0194-8
Zakharchenko BV, Khomenko DM, Doroshchuk RO, Raspertova IV, Starova VS, Trachevsky VV, Shova S, Severynovska OV, Martins LMDRS, Pombeiro AJL, Arion VB, Lampeka RD (2019) New palladium(II) complexes with 3-(2-pyridyl)-5-alkyl-1,2,4-triazole ligands as recyclable C–C coupling catalysts. New J Chem 43:10973–10984. https://doi.org/10.1039/C9NJ02278C
Zhang J, Zhang F, Li H, Liu C, Xia J, Ma L, Chu W, Zhang Z, Chen C, Li S, Wang S (2012) Recent progress and future potential for metal complexes as anticancer drugs targeting G-quadruplex DNA. Curr Med Chem 19(18):2957–2975. https://doi.org/10.2174/092986712800672067
Acknowledgements
We thank Dr. F. Lopez-Ortiz for experimental assistance in taking multinuclear (1H, 13C, 15N) NMR spectra. This work was supported by a grant of Romanian Ministry of Research and Innovation, CNCS—UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0050 (5DnanoP), within PNCDI III.
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Zakharchenko, B.V., Khomenko, D.M., Doroschuk, R.O. et al. Cis-Palladium(II) complex incorporating 3-(2-pyridyl)-5-methyl-1,2,4-triazole: structure and cytotoxic activity. Chem. Pap. 75, 4899–4906 (2021). https://doi.org/10.1007/s11696-021-01699-4
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DOI: https://doi.org/10.1007/s11696-021-01699-4