Preparation, structure and cytotoxicity of cis-diammineplatinum(II) dinuclear complexes with 1-alkyluracil and imidate ligands

Yukifumi Dohta, Scott Browning, Petri Rekonen, Masato Kodaka, Tomoko Okada, Ken-Ichi Okamoto, Rosanne Natale, Carol Yip, David Farrar, Hiroaki Okuno

Research output: Contribution to journalArticleScientificpeer-review

16 Citations (Scopus)

Abstract

A series of platinum dinuclear complexes with l-alkyluracil, cis-[Ph2(PtU)2(NH3)4] (NO3)2, cis-[Pt2(n-BuU)2(NH3)4](NO3)2, cis-[Ph2(BzlU)2(NH3)4](NO3)2 and cis-[Pt2(NaphCH2U)2(NH3)4](NO3)2 (head-to-head, where U=uracil), and with imide ligands, cis-[Ph2(SI2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-tail) and cis-[Pt2(DMGI)2(NH3)4] (NO3)2 (head-to-head, where SI = succinimidate, EMGI = 3-ethyl-3-methylglutarimidate and DMGi=3,3.dimethylglutarimidate) was synthesized, as well as platinum mononuelear complexes, cis-[PtCl(SI)(NH3)2] and cis- [Pt(SI)2(NH3)2]. The isomers of the dinuclear complexes (head-to-head and head-to-tail forms) were obtained separately by fractional recystallizations. Crystal structures of cis-[Pt2(SI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head) and cis-[Pt2(EMGI)2(NH3)4](NO3)2 (head-to-head) were determined by X-ray diffraction analysis. Cytotoxic activity was evaluated by the IC50 value using mouse sarcoma S-180 cells. Most head-to-head complexes are considerably active, while the corresponding head-to-tail analogues are inactive. The active complexes, in general, release ligands in saline at 37°C, and a relationship between hydrophobicity of the complexes and the IC50 value has been shown.

Original languageEnglish
Pages (from-to)69 - 79
Number of pages11
JournalInorganica Chimica Acta
Volume263
Issue number1-2
DOIs
Publication statusPublished - 1997
MoE publication typeA1 Journal article-refereed

Fingerprint

Imidoesters
International System of Units
Cytotoxicity
Platinum
Ligands
Imides
preparation
ligands
Uracil
Hydrophobicity
Isomers
X ray diffraction analysis
platinum
Crystal structure
uracil
imides
hydrophobicity
mice
isomers
cancer

Cite this

Dohta, Yukifumi ; Browning, Scott ; Rekonen, Petri ; Kodaka, Masato ; Okada, Tomoko ; Okamoto, Ken-Ichi ; Natale, Rosanne ; Yip, Carol ; Farrar, David ; Okuno, Hiroaki. / Preparation, structure and cytotoxicity of cis-diammineplatinum(II) dinuclear complexes with 1-alkyluracil and imidate ligands. In: Inorganica Chimica Acta. 1997 ; Vol. 263, No. 1-2. pp. 69 - 79.
@article{086507e77d4e475c828f7420a9d65726,
title = "Preparation, structure and cytotoxicity of cis-diammineplatinum(II) dinuclear complexes with 1-alkyluracil and imidate ligands",
abstract = "A series of platinum dinuclear complexes with l-alkyluracil, cis-[Ph2(PtU)2(NH3)4] (NO3)2, cis-[Pt2(n-BuU)2(NH3)4](NO3)2, cis-[Ph2(BzlU)2(NH3)4](NO3)2 and cis-[Pt2(NaphCH2U)2(NH3)4](NO3)2 (head-to-head, where U=uracil), and with imide ligands, cis-[Ph2(SI2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-tail) and cis-[Pt2(DMGI)2(NH3)4] (NO3)2 (head-to-head, where SI = succinimidate, EMGI = 3-ethyl-3-methylglutarimidate and DMGi=3,3.dimethylglutarimidate) was synthesized, as well as platinum mononuelear complexes, cis-[PtCl(SI)(NH3)2] and cis- [Pt(SI)2(NH3)2]. The isomers of the dinuclear complexes (head-to-head and head-to-tail forms) were obtained separately by fractional recystallizations. Crystal structures of cis-[Pt2(SI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head) and cis-[Pt2(EMGI)2(NH3)4](NO3)2 (head-to-head) were determined by X-ray diffraction analysis. Cytotoxic activity was evaluated by the IC50 value using mouse sarcoma S-180 cells. Most head-to-head complexes are considerably active, while the corresponding head-to-tail analogues are inactive. The active complexes, in general, release ligands in saline at 37°C, and a relationship between hydrophobicity of the complexes and the IC50 value has been shown.",
author = "Yukifumi Dohta and Scott Browning and Petri Rekonen and Masato Kodaka and Tomoko Okada and Ken-Ichi Okamoto and Rosanne Natale and Carol Yip and David Farrar and Hiroaki Okuno",
note = "Project code: K7SU00052",
year = "1997",
doi = "10.1016/S0020-1693(97)05568-0",
language = "English",
volume = "263",
pages = "69 -- 79",
journal = "Inorganica Chimica Acta",
issn = "0020-1693",
publisher = "Elsevier",
number = "1-2",

}

Dohta, Y, Browning, S, Rekonen, P, Kodaka, M, Okada, T, Okamoto, K-I, Natale, R, Yip, C, Farrar, D & Okuno, H 1997, 'Preparation, structure and cytotoxicity of cis-diammineplatinum(II) dinuclear complexes with 1-alkyluracil and imidate ligands', Inorganica Chimica Acta, vol. 263, no. 1-2, pp. 69 - 79. https://doi.org/10.1016/S0020-1693(97)05568-0

Preparation, structure and cytotoxicity of cis-diammineplatinum(II) dinuclear complexes with 1-alkyluracil and imidate ligands. / Dohta, Yukifumi; Browning, Scott; Rekonen, Petri; Kodaka, Masato; Okada, Tomoko; Okamoto, Ken-Ichi; Natale, Rosanne; Yip, Carol; Farrar, David; Okuno, Hiroaki.

In: Inorganica Chimica Acta, Vol. 263, No. 1-2, 1997, p. 69 - 79.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Preparation, structure and cytotoxicity of cis-diammineplatinum(II) dinuclear complexes with 1-alkyluracil and imidate ligands

AU - Dohta, Yukifumi

AU - Browning, Scott

AU - Rekonen, Petri

AU - Kodaka, Masato

AU - Okada, Tomoko

AU - Okamoto, Ken-Ichi

AU - Natale, Rosanne

AU - Yip, Carol

AU - Farrar, David

AU - Okuno, Hiroaki

N1 - Project code: K7SU00052

PY - 1997

Y1 - 1997

N2 - A series of platinum dinuclear complexes with l-alkyluracil, cis-[Ph2(PtU)2(NH3)4] (NO3)2, cis-[Pt2(n-BuU)2(NH3)4](NO3)2, cis-[Ph2(BzlU)2(NH3)4](NO3)2 and cis-[Pt2(NaphCH2U)2(NH3)4](NO3)2 (head-to-head, where U=uracil), and with imide ligands, cis-[Ph2(SI2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-tail) and cis-[Pt2(DMGI)2(NH3)4] (NO3)2 (head-to-head, where SI = succinimidate, EMGI = 3-ethyl-3-methylglutarimidate and DMGi=3,3.dimethylglutarimidate) was synthesized, as well as platinum mononuelear complexes, cis-[PtCl(SI)(NH3)2] and cis- [Pt(SI)2(NH3)2]. The isomers of the dinuclear complexes (head-to-head and head-to-tail forms) were obtained separately by fractional recystallizations. Crystal structures of cis-[Pt2(SI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head) and cis-[Pt2(EMGI)2(NH3)4](NO3)2 (head-to-head) were determined by X-ray diffraction analysis. Cytotoxic activity was evaluated by the IC50 value using mouse sarcoma S-180 cells. Most head-to-head complexes are considerably active, while the corresponding head-to-tail analogues are inactive. The active complexes, in general, release ligands in saline at 37°C, and a relationship between hydrophobicity of the complexes and the IC50 value has been shown.

AB - A series of platinum dinuclear complexes with l-alkyluracil, cis-[Ph2(PtU)2(NH3)4] (NO3)2, cis-[Pt2(n-BuU)2(NH3)4](NO3)2, cis-[Ph2(BzlU)2(NH3)4](NO3)2 and cis-[Pt2(NaphCH2U)2(NH3)4](NO3)2 (head-to-head, where U=uracil), and with imide ligands, cis-[Ph2(SI2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-tail) and cis-[Pt2(DMGI)2(NH3)4] (NO3)2 (head-to-head, where SI = succinimidate, EMGI = 3-ethyl-3-methylglutarimidate and DMGi=3,3.dimethylglutarimidate) was synthesized, as well as platinum mononuelear complexes, cis-[PtCl(SI)(NH3)2] and cis- [Pt(SI)2(NH3)2]. The isomers of the dinuclear complexes (head-to-head and head-to-tail forms) were obtained separately by fractional recystallizations. Crystal structures of cis-[Pt2(SI)2(NH3)4](NO3)2 (head-to-head), cis-[Pt2(DMGI)2(NH3)4](NO3)2 (head-to-head) and cis-[Pt2(EMGI)2(NH3)4](NO3)2 (head-to-head) were determined by X-ray diffraction analysis. Cytotoxic activity was evaluated by the IC50 value using mouse sarcoma S-180 cells. Most head-to-head complexes are considerably active, while the corresponding head-to-tail analogues are inactive. The active complexes, in general, release ligands in saline at 37°C, and a relationship between hydrophobicity of the complexes and the IC50 value has been shown.

U2 - 10.1016/S0020-1693(97)05568-0

DO - 10.1016/S0020-1693(97)05568-0

M3 - Article

VL - 263

SP - 69

EP - 79

JO - Inorganica Chimica Acta

JF - Inorganica Chimica Acta

SN - 0020-1693

IS - 1-2

ER -