Synthesis and Structure of a New Thiazoline-based Palladium(II) Complex That Promotes Cytotoxicity and Apoptosis of Human Promyelocytic Leukemia HL-60 Cells

Overview

Journal Sci Rep

Specialty Science

Date 2020 Oct 8

PMID 33028870

Citations 8

Authors

Javier Espino

Elena Fernandez-Delgado

Samuel Estirado

Felipe de la Cruz-Martinez

Sergio Villa-Carballar

Emilio Vinuelas-Zahinos

Francisco Luna-Giles

Jose A Pariente

Affiliations

Soon will be listed here.

Abstract

Cisplatin is one of the most widely used chemotherapeutic agents in the treatment of different tumors but has high toxicity and side effects. Therefore, the synthesis of new chemotherapeutic agents is necessary, so that they are effective in the treatment of cancer while avoiding such toxicity. In this study, we have synthesized and characterized a palladium(II) complex, [PdCl(µ-PyTT)]Cl·4HO (PdPyTT), with 2-(2-pyridyl)imine-N-(2-thiazolin-2-yl)thiazolidine (PyTT) as a ligand; besides, its cytotoxicity and pro-apoptotic capacity was tested in human promyelocytic leukemia HL-60 cell line. Similar to cisplatin, PdPyTT produced a time- and dose-dependent decrease in cell viability. Additionally, the palladium complex increased both the proportion of cells with apoptotic morphology and the activation of caspase-3 and -9. PdPyTT, like cisplatin, also increased intracellular ROS production and DNA oxidative damage. Therefore, our findings demonstrated the promising application of palladium(II) complexes as novel anti-leukemic agents.

Citing Articles

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References

Zivanovic M, Kosaric J, Smit B, Seklic D, Pavlovic R, Markovic S . Novel seleno-hydantoin palladium(II) complex - antimigratory, cytotoxic and prooxidative potential on human colon HCT-116 and breast MDA-MB-231 cancer cells. Gen Physiol Biophys. 2017; 36(2):187-196. DOI: 10.4149/gpb_2016036. View

Han F, Osajima H, Cheung M, Tokuyama H, Fukuyama T . Novel structural motifs consisting of chiral thiazolines: synthesis, molecular recognition, and anticancer activity. Chemistry. 2007; 13(11):3026-38. DOI: 10.1002/chem.200601446. View

Cocic D, Jovanovic S, Nisavic M, Baskic D, Todorovic D, Popovic S . New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity. J Inorg Biochem. 2017; 175:67-79. DOI: 10.1016/j.jinorgbio.2017.07.009. View

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View

Cetin Y, Adiguzel Z, Polat H, Akkoc T, Tas A, Cevatemre B . A palladium(II)-saccharinate complex of terpyridine exerts higher anticancer potency and less toxicity than cisplatin in a mouse allograft model. Anticancer Drugs. 2017; 28(8):898-910. DOI: 10.1097/CAD.0000000000000531. View

Romagnoli R, Baraldi P, Salvador M, Camacho M, Balzarini J, Bermejo J . Anticancer activity of novel hybrid molecules containing 5-benzylidene thiazolidine-2,4-dione. Eur J Med Chem. 2013; 63:544-57. DOI: 10.1016/j.ejmech.2013.02.030. View

Chaviara A, Christidis P, Papageorgiou A, Chrysogelou E, Hadjipavlou-Litina D, Bolos C . In vivo anticancer, anti-inflammatory, and toxicity studies of mixed-ligand Cu(II) complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino-2-thiazoline. Crystal structure of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O). J Inorg Biochem. 2005; 99(11):2102-9. DOI: 10.1016/j.jinorgbio.2005.07.011. View

Tanaka M, Kataoka H, Yano S, Ohi H, Kawamoto K, Shibahara T . Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells. BMC Cancer. 2013; 13:237. PMC: 3659059. DOI: 10.1186/1471-2407-13-237. View

Oehninger L, Rubbiani R, Ott I . N-Heterocyclic carbene metal complexes in medicinal chemistry. Dalton Trans. 2012; 42(10):3269-84. DOI: 10.1039/c2dt32617e. View

10.

Kapdi A, Fairlamb I . Anti-cancer palladium complexes: a focus on PdX2L2, palladacycles and related complexes. Chem Soc Rev. 2014; 43(13):4751-77. DOI: 10.1039/c4cs00063c. View

11.

Iglesias-Figueroa B, Siqueiros-Cendon T, Gutierrez D, Aguilera R, Espinoza-Sanchez E, Arevalo-Gallegos S . Recombinant human lactoferrin induces apoptosis, disruption of F-actin structure and cell cycle arrest with selective cytotoxicity on human triple negative breast cancer cells. Apoptosis. 2019; 24(7-8):562-577. PMC: 8935999. DOI: 10.1007/s10495-019-01539-7. View

12.

Shafaatian B, Soleymanpour A, Kholghi Oskouei N, Notash B, Rezvani S . Synthesis, crystal structure, fluorescence and electrochemical studies of a new tridentate Schiff base ligand and its nickel(II) and palladium(II) complexes. Spectrochim Acta A Mol Biomol Spectrosc. 2014; 128:363-9. DOI: 10.1016/j.saa.2014.02.179. View

13.

Gasser G, Ott I, Metzler-Nolte N . Organometallic anticancer compounds. J Med Chem. 2010; 54(1):3-25. PMC: 3018145. DOI: 10.1021/jm100020w. View

14.

Fulda S, Debatin K . Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006; 25(34):4798-811. DOI: 10.1038/sj.onc.1209608. View

15.

Kuduk-Jaworska J, Puszko A, Kubiak M, Pelczynska M . Synthesis, structural, physico-chemical and biological properties of new palladium(II) complexes with 2,6-dimethyl-4-nitropyridine. J Inorg Biochem. 2004; 98(8):1447-56. DOI: 10.1016/j.jinorgbio.2004.05.008. View

16.

Santos R, Correia S, Zhu X, Smith M, Moreira P, Castellani R . Mitochondrial DNA oxidative damage and repair in aging and Alzheimer's disease. Antioxid Redox Signal. 2012; 18(18):2444-57. PMC: 3671662. DOI: 10.1089/ars.2012.5039. View

17.

Robles-Escajeda E, Lerma D, Nyakeriga A, Ross J, Kirken R, Aguilera R . Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells. PLoS One. 2013; 8(9):e73508. PMC: 3767772. DOI: 10.1371/journal.pone.0073508. View

18.

Bolos C, Papazisis K, Kortsaris A, Voyatzi S, Zambouli D, Kyriakidis D . Antiproliferative activity of mixed-ligand dien-Cu(II) complexes with thiazole, thiazoline and imidazole derivatives. J Inorg Biochem. 2001; 88(1):25-36. DOI: 10.1016/s0162-0134(01)00344-0. View

19.

Bernalte-Garcia A, Garcia-Barros F, Higes-Rolando F, Luna-Giles F, Pacheco-Rodriguez M, Vinuelas-Zahinos E . Synthesis and characterization of a new cobalt(II) complex with 2-(2-pyridyl)imino-N-(2-thiazolin-2-yl)thiazolidine (PyTT). Bioinorg Chem Appl. 2008; :307-16. PMC: 2267081. DOI: 10.1155/S1565363304000184. View

20.

Villanueva P, Martinez A, Baca S, DeJesus R, Larragoity M, Contreras L . Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis. PLoS One. 2018; 13(11):e0206467. PMC: 6218039. DOI: 10.1371/journal.pone.0206467. View