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New platinum–oxicam complexes as anti-cancer drugs. Synthesis, characterization, release studies from smart hydrogels, evaluation of reactivity with selected proteins and cytotoxic activity in vitro

New platinum–oxicam complexes as anti-cancer drugs. Synthesis, characterization, release studies from smart hydrogels, evaluation of reactivity with selected proteins and cytotoxic activity in vitro
New platinum–oxicam complexes as anti-cancer drugs. Synthesis, characterization, release studies from smart hydrogels, evaluation of reactivity with selected proteins and cytotoxic activity in vitro
The reaction of aqueous cis-[Pt(NH(3))(2)(H(2)O)(2)](NO(3))(2) with Na(+)HMEL(-) (H(2)MEL, meloxicam, 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide), and Na(+)HISO(-)(H(2)ISO, isoxicam, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) at pH 7 produced micro-crystalline cis-[Pt(NH(3))(2)((N) under bar (1)'-HMEL)(2)], 5 and cis-[Pt(NH(3))(2)((N) under bar (1)'-HISO)(2)], 6. The X-ray diffraction structure of 5 shows two HMEL(-) anions donating through the thiazole nitrogen atoms and adopting a head-to-tail (HT) conformation. The (1)H NMR spectrum for 5 from DMSO-d(6) shows inertness of the complex up to at least 24 h. Delivery studies for 5 and 6 from vinyl hydrogel based on L-phenylalanine (pH 6.5, 25 degrees C) show that concentrations of complexes ranging between 2.5 and 5 mu M can be reached after a day. Compounds 5 and 6 show strong anti-proliferative effects on CH1 cells (ovarian carcinoma, human) in vitro. IC(50) values being 0.60 and 0.37 mu M, respectively (0.16 mu M for reference, cis-diamminodichloridoplatinum(II), cisplatin). ESI-MS measurements clearly documented that both 5 and 6 form adducts with the three model proteins ubiquitin (UBI), cytochrome c (CYT C) and superoxide dismutase (SOD), the HISO(-) complex being significantly more effective than the HMEL(-) one. Density functional methods help in finding rationale for the easiest dissociation of Pt-H(2)ISO/HISO bonds when compared to the Pt-(N) under bar (1)'-H(2)MEL/(N) under bar (1)'-HMEL linkages.
0162-0134
799-814
Tamasi, Gabriella
505d1a4c-a30d-4c0e-ab97-d80d7f71d1e2
Casolaro, Mario
db6aaa44-010c-4829-b1f8-bd8aaa4a7e4f
Magnani, Agnese
53a78c4b-7d9f-4f7b-a3c2-5dcc2418f979
Sega, Alessandro
1acf46ce-1402-45cf-a8fa-d077e62f5a5a
Chiasserini, Luisa
fa34e25c-6eeb-4214-bb32-66a0f48eb810
Messori, Luigi
82015012-2a23-4173-919e-1c848720ed09
Gabbiani, Chiara
ea7f8189-f280-4537-b3ad-d3dda3e6703f
Valiahdi, Seied Mojtaba
4428e0be-72d0-436d-9ca8-1ed6712bc3db
Jakupec, Michael A.
a53c9561-1cf0-4acb-b23a-f88d848210cd
Keppler, Bernhard K.
fb7991d8-a4d4-4a83-a4b1-aeb78ca02e32
Hursthouse, Michael B.
57a2ddf9-b1b3-4f38-bfe9-ef2f526388da
Cini, Renzo
86fac752-2120-4f92-932e-b33e3580fdc0
Tamasi, Gabriella
505d1a4c-a30d-4c0e-ab97-d80d7f71d1e2
Casolaro, Mario
db6aaa44-010c-4829-b1f8-bd8aaa4a7e4f
Magnani, Agnese
53a78c4b-7d9f-4f7b-a3c2-5dcc2418f979
Sega, Alessandro
1acf46ce-1402-45cf-a8fa-d077e62f5a5a
Chiasserini, Luisa
fa34e25c-6eeb-4214-bb32-66a0f48eb810
Messori, Luigi
82015012-2a23-4173-919e-1c848720ed09
Gabbiani, Chiara
ea7f8189-f280-4537-b3ad-d3dda3e6703f
Valiahdi, Seied Mojtaba
4428e0be-72d0-436d-9ca8-1ed6712bc3db
Jakupec, Michael A.
a53c9561-1cf0-4acb-b23a-f88d848210cd
Keppler, Bernhard K.
fb7991d8-a4d4-4a83-a4b1-aeb78ca02e32
Hursthouse, Michael B.
57a2ddf9-b1b3-4f38-bfe9-ef2f526388da
Cini, Renzo
86fac752-2120-4f92-932e-b33e3580fdc0

Tamasi, Gabriella, Casolaro, Mario, Magnani, Agnese, Sega, Alessandro, Chiasserini, Luisa, Messori, Luigi, Gabbiani, Chiara, Valiahdi, Seied Mojtaba, Jakupec, Michael A., Keppler, Bernhard K., Hursthouse, Michael B. and Cini, Renzo (2010) New platinum–oxicam complexes as anti-cancer drugs. Synthesis, characterization, release studies from smart hydrogels, evaluation of reactivity with selected proteins and cytotoxic activity in vitro. Journal of Inorganic Biochemistry, 104 (8), 799-814. (doi:10.1016/j.jinorgbio.2010.03.010). (PMID:20447694)

Record type: Article

Abstract

The reaction of aqueous cis-[Pt(NH(3))(2)(H(2)O)(2)](NO(3))(2) with Na(+)HMEL(-) (H(2)MEL, meloxicam, 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide), and Na(+)HISO(-)(H(2)ISO, isoxicam, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) at pH 7 produced micro-crystalline cis-[Pt(NH(3))(2)((N) under bar (1)'-HMEL)(2)], 5 and cis-[Pt(NH(3))(2)((N) under bar (1)'-HISO)(2)], 6. The X-ray diffraction structure of 5 shows two HMEL(-) anions donating through the thiazole nitrogen atoms and adopting a head-to-tail (HT) conformation. The (1)H NMR spectrum for 5 from DMSO-d(6) shows inertness of the complex up to at least 24 h. Delivery studies for 5 and 6 from vinyl hydrogel based on L-phenylalanine (pH 6.5, 25 degrees C) show that concentrations of complexes ranging between 2.5 and 5 mu M can be reached after a day. Compounds 5 and 6 show strong anti-proliferative effects on CH1 cells (ovarian carcinoma, human) in vitro. IC(50) values being 0.60 and 0.37 mu M, respectively (0.16 mu M for reference, cis-diamminodichloridoplatinum(II), cisplatin). ESI-MS measurements clearly documented that both 5 and 6 form adducts with the three model proteins ubiquitin (UBI), cytochrome c (CYT C) and superoxide dismutase (SOD), the HISO(-) complex being significantly more effective than the HMEL(-) one. Density functional methods help in finding rationale for the easiest dissociation of Pt-H(2)ISO/HISO bonds when compared to the Pt-(N) under bar (1)'-H(2)MEL/(N) under bar (1)'-HMEL linkages.

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Published date: August 2010
Organisations: Organic Chemistry: Synthesis, Catalysis and Flow

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Local EPrints ID: 347463
URI: http://eprints.soton.ac.uk/id/eprint/347463
ISSN: 0162-0134
PURE UUID: 2aae1c43-f1d5-4668-8e0c-a57021f3d117

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Date deposited: 23 Jan 2013 12:00
Last modified: 14 Mar 2024 12:48

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Contributors

Author: Gabriella Tamasi
Author: Mario Casolaro
Author: Agnese Magnani
Author: Alessandro Sega
Author: Luisa Chiasserini
Author: Luigi Messori
Author: Chiara Gabbiani
Author: Seied Mojtaba Valiahdi
Author: Michael A. Jakupec
Author: Bernhard K. Keppler
Author: Renzo Cini

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