Amidoxime platinum(II) complexes: pH-dependent highly selective generation and cytotoxic activity

Dmitrii S. Bolotin; Marina Ya. Demakova; Anton A. Legin; Vitaliy V. Suslonov; Alexey A. Nazarov; Michael A. Jakupec; Bernhard K. Keppler; Vadim Yu Kukushkin

doi:10.1039/c7nj00982h

Amidoxime platinum(II) complexes: pH-dependent highly selective generation and cytotoxic activity

Dmitrii S. Bolotin (Corresponding author), Marina Ya. Demakova, Anton A. Legin, Vitaliy V. Suslonov, Alexey A. Nazarov, Michael A. Jakupec (Corresponding author), Bernhard K. Keppler, Vadim Yu Kukushkin

Department of Inorganic Chemistry

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

The reaction of cis-[PtCl ₂(Me ₂SO) ₂] with 1 equiv. of each of the amidoximes RC(NH ₂)NOH in neutral media in MeOH results in the formation of complexes cis-[PtCl ₂{RC(NH ₂)NOH}(Me ₂SO)] (5 examples; 83-98% isolated yields). In the presence of 2 equiv. of NaOH in MeOH solution, the reaction of cis-[PtCl ₂(Me ₂SO) ₂] with 1 equiv. of each of the amidoximes RC(NH ₂)NOH leads to [Pt{RC(NH)NO}(Me ₂SO) ₂] (7 examples; 74-95% isolated yields). All new complexes were characterized by C, H, and N elemental analyses, HRESI ⁺-MS, IR, ¹H, ¹³C{ ¹H}, and CP-MAS TOSS ¹³C{ ¹H} NMR spectroscopies, and additionally by single-crystal XRD (for seven species). The cytotoxic potency of six compounds was determined in the human cancer cell lines CH1/PA-1, A549, SK-BR-3, and SW480. Generally, the second class of complexes containing chelating amidoximato ligands shows much higher cytotoxicity than the non-chelate amidoxime analogs, despite the lack of easily exchangeable chlorido ligands. Especially, the complex [Pt(p-CF ₃C ₆H ₄C(NH)NO)(Me ₂SO) ₂] displays a remarkable activity in the inherently cisplatin resistant SW480 cell line (0.51 μM vs. 3.3 μM).

Original language	English
Pages (from-to)	6840-6848
Number of pages	9
Journal	New Journal of Chemistry
Volume	41
Issue number	14
DOIs	https://doi.org/10.1039/c7nj00982h
Publication status	Published - 21 Jul 2017

Austrian Fields of Science 2012

104003 Inorganic chemistry
301904 Cancer research

Keywords

VITRO ANTICANCER ACTIVITY
OXIME LIGANDS
STRUCTURAL-CHARACTERIZATION
NEXT-GENERATION
DRUGS
AGENTS
DMSO
1,2,4-OXADIAZOLES
PALLADIUM(II)
CISPLATIN

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1039/c7nj00982h

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@article{2b9bbd0fb2794e7582a4d3b0fbbec89d,

title = "Amidoxime platinum(II) complexes: pH-dependent highly selective generation and cytotoxic activity",

abstract = "The reaction of cis-[PtCl 2(Me 2SO) 2] with 1 equiv. of each of the amidoximes RC(NH 2)NOH in neutral media in MeOH results in the formation of complexes cis-[PtCl 2{RC(NH 2)NOH}(Me 2SO)] (5 examples; 83-98% isolated yields). In the presence of 2 equiv. of NaOH in MeOH solution, the reaction of cis-[PtCl 2(Me 2SO) 2] with 1 equiv. of each of the amidoximes RC(NH 2)NOH leads to [Pt{RC(NH)NO}(Me 2SO) 2] (7 examples; 74-95% isolated yields). All new complexes were characterized by C, H, and N elemental analyses, HRESI +-MS, IR, 1H, 13C{ 1H}, and CP-MAS TOSS 13C{ 1H} NMR spectroscopies, and additionally by single-crystal XRD (for seven species). The cytotoxic potency of six compounds was determined in the human cancer cell lines CH1/PA-1, A549, SK-BR-3, and SW480. Generally, the second class of complexes containing chelating amidoximato ligands shows much higher cytotoxicity than the non-chelate amidoxime analogs, despite the lack of easily exchangeable chlorido ligands. Especially, the complex [Pt(p-CF 3C 6H 4C(NH)NO)(Me 2SO) 2] displays a remarkable activity in the inherently cisplatin resistant SW480 cell line (0.51 μM vs. 3.3 μM). ",

keywords = "VITRO ANTICANCER ACTIVITY, OXIME LIGANDS, STRUCTURAL-CHARACTERIZATION, NEXT-GENERATION, DRUGS, AGENTS, DMSO, 1,2,4-OXADIAZOLES, PALLADIUM(II), CISPLATIN",

author = "Bolotin, {Dmitrii S.} and Demakova, {Marina Ya.} and Legin, {Anton A.} and Suslonov, {Vitaliy V.} and Nazarov, {Alexey A.} and Jakupec, {Michael A.} and Keppler, {Bernhard K.} and Kukushkin, {Vadim Yu}",

note = "Publisher Copyright: {\textcopyright} 2017 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.",

year = "2017",

month = jul,

day = "21",

doi = "10.1039/c7nj00982h",

language = "English",

volume = "41",

pages = "6840--6848",

journal = "New Journal of Chemistry",

issn = "1144-0546",

publisher = "ROYAL SOC CHEMISTRY",

number = "14",

}

TY - JOUR

T1 - Amidoxime platinum(II) complexes

T2 - pH-dependent highly selective generation and cytotoxic activity

AU - Bolotin, Dmitrii S.

AU - Demakova, Marina Ya.

AU - Legin, Anton A.

AU - Suslonov, Vitaliy V.

AU - Nazarov, Alexey A.

AU - Jakupec, Michael A.

AU - Keppler, Bernhard K.

AU - Kukushkin, Vadim Yu

PY - 2017/7/21

Y1 - 2017/7/21

N2 - The reaction of cis-[PtCl 2(Me 2SO) 2] with 1 equiv. of each of the amidoximes RC(NH 2)NOH in neutral media in MeOH results in the formation of complexes cis-[PtCl 2{RC(NH 2)NOH}(Me 2SO)] (5 examples; 83-98% isolated yields). In the presence of 2 equiv. of NaOH in MeOH solution, the reaction of cis-[PtCl 2(Me 2SO) 2] with 1 equiv. of each of the amidoximes RC(NH 2)NOH leads to [Pt{RC(NH)NO}(Me 2SO) 2] (7 examples; 74-95% isolated yields). All new complexes were characterized by C, H, and N elemental analyses, HRESI +-MS, IR, 1H, 13C{ 1H}, and CP-MAS TOSS 13C{ 1H} NMR spectroscopies, and additionally by single-crystal XRD (for seven species). The cytotoxic potency of six compounds was determined in the human cancer cell lines CH1/PA-1, A549, SK-BR-3, and SW480. Generally, the second class of complexes containing chelating amidoximato ligands shows much higher cytotoxicity than the non-chelate amidoxime analogs, despite the lack of easily exchangeable chlorido ligands. Especially, the complex [Pt(p-CF 3C 6H 4C(NH)NO)(Me 2SO) 2] displays a remarkable activity in the inherently cisplatin resistant SW480 cell line (0.51 μM vs. 3.3 μM).

AB - The reaction of cis-[PtCl 2(Me 2SO) 2] with 1 equiv. of each of the amidoximes RC(NH 2)NOH in neutral media in MeOH results in the formation of complexes cis-[PtCl 2{RC(NH 2)NOH}(Me 2SO)] (5 examples; 83-98% isolated yields). In the presence of 2 equiv. of NaOH in MeOH solution, the reaction of cis-[PtCl 2(Me 2SO) 2] with 1 equiv. of each of the amidoximes RC(NH 2)NOH leads to [Pt{RC(NH)NO}(Me 2SO) 2] (7 examples; 74-95% isolated yields). All new complexes were characterized by C, H, and N elemental analyses, HRESI +-MS, IR, 1H, 13C{ 1H}, and CP-MAS TOSS 13C{ 1H} NMR spectroscopies, and additionally by single-crystal XRD (for seven species). The cytotoxic potency of six compounds was determined in the human cancer cell lines CH1/PA-1, A549, SK-BR-3, and SW480. Generally, the second class of complexes containing chelating amidoximato ligands shows much higher cytotoxicity than the non-chelate amidoxime analogs, despite the lack of easily exchangeable chlorido ligands. Especially, the complex [Pt(p-CF 3C 6H 4C(NH)NO)(Me 2SO) 2] displays a remarkable activity in the inherently cisplatin resistant SW480 cell line (0.51 μM vs. 3.3 μM).

KW - VITRO ANTICANCER ACTIVITY

KW - OXIME LIGANDS

KW - STRUCTURAL-CHARACTERIZATION

KW - NEXT-GENERATION

KW - DRUGS

KW - AGENTS

KW - DMSO

KW - 1,2,4-OXADIAZOLES

KW - PALLADIUM(II)

KW - CISPLATIN

UR - http://www.scopus.com/inward/record.url?scp=85023202747&partnerID=8YFLogxK

U2 - 10.1039/c7nj00982h

DO - 10.1039/c7nj00982h

M3 - Article

VL - 41

SP - 6840

EP - 6848

JO - New Journal of Chemistry

JF - New Journal of Chemistry

SN - 1144-0546

IS - 14

ER -

Amidoxime platinum(II) complexes: pH-dependent highly selective generation and cytotoxic activity

Abstract

Austrian Fields of Science 2012

Keywords

UN SDGs

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