Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes

Young A. Lee; Sung Sil Lee; Kwan Mook Kim; Chong Ock Lee; Youn Soo Sohn

doi:10.1021/jm9904250

Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes

Young A. Lee, Sung Sil Lee, Kwan Mook Kim, Chong Ock Lee, Youn Soo Sohn

Department of Chemistry & Nanoscience

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O₂CR)₄(dach)] (dach = trans(±)-1,2-diaminocyclohexane; R = C(n)H(2n+1), n = 1 ~ 5), was synthesized and studied for physicochemical properties and oral antitumor activity. Lipophilicity and aqueous solubility of the title complexes were greatly dependent on the alkyl chain length of the carboxylate ligand, and their partition coefficient and solubility changed by 4 or 5 orders of magnitude from acetate to hexanoate complexes. On the other hand, the range of their cathodic reduction potential (-546 ~ -403 mV) depending on the chain length of the carboxylate ligand was relatively small. Among the title complexes, the tetrakis(propionato)platinum(IV) complex, [Pt(O₂CC₂H₅)₄(dach)], with appropriate lipophilicity (log P = 0.18) and aqueous solubility (14.6 mg/mL) was found to exhibit better oral antitumor activity than JM216 against the human ovarian tumor xenograft SKOV3 in nude mice.

Original language	English
Pages (from-to)	1409-1412
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	43
Issue number	7
DOIs	https://doi.org/10.1021/jm9904250
State	Published - 6 Apr 2000

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@article{23eabe72895b4a0d84986cddb45eb61a,

title = "Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes",

abstract = "A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O2CR)4(dach)] (dach = trans(±)-1,2-diaminocyclohexane; R = C(n)H(2n+1), n = 1 ~ 5), was synthesized and studied for physicochemical properties and oral antitumor activity. Lipophilicity and aqueous solubility of the title complexes were greatly dependent on the alkyl chain length of the carboxylate ligand, and their partition coefficient and solubility changed by 4 or 5 orders of magnitude from acetate to hexanoate complexes. On the other hand, the range of their cathodic reduction potential (-546 ~ -403 mV) depending on the chain length of the carboxylate ligand was relatively small. Among the title complexes, the tetrakis(propionato)platinum(IV) complex, [Pt(O2CC2H5)4(dach)], with appropriate lipophilicity (log P = 0.18) and aqueous solubility (14.6 mg/mL) was found to exhibit better oral antitumor activity than JM216 against the human ovarian tumor xenograft SKOV3 in nude mice.",

author = "Lee, {Young A.} and Lee, {Sung Sil} and Kim, {Kwan Mook} and Lee, {Chong Ock} and Sohn, {Youn Soo}",

year = "2000",

month = apr,

day = "6",

doi = "10.1021/jm9904250",

language = "English",

volume = "43",

pages = "1409--1412",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "7",

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TY - JOUR

T1 - Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes

AU - Lee, Young A.

AU - Lee, Sung Sil

AU - Kim, Kwan Mook

AU - Lee, Chong Ock

AU - Sohn, Youn Soo

PY - 2000/4/6

Y1 - 2000/4/6

N2 - A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O2CR)4(dach)] (dach = trans(±)-1,2-diaminocyclohexane; R = C(n)H(2n+1), n = 1 ~ 5), was synthesized and studied for physicochemical properties and oral antitumor activity. Lipophilicity and aqueous solubility of the title complexes were greatly dependent on the alkyl chain length of the carboxylate ligand, and their partition coefficient and solubility changed by 4 or 5 orders of magnitude from acetate to hexanoate complexes. On the other hand, the range of their cathodic reduction potential (-546 ~ -403 mV) depending on the chain length of the carboxylate ligand was relatively small. Among the title complexes, the tetrakis(propionato)platinum(IV) complex, [Pt(O2CC2H5)4(dach)], with appropriate lipophilicity (log P = 0.18) and aqueous solubility (14.6 mg/mL) was found to exhibit better oral antitumor activity than JM216 against the human ovarian tumor xenograft SKOV3 in nude mice.

AB - A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O2CR)4(dach)] (dach = trans(±)-1,2-diaminocyclohexane; R = C(n)H(2n+1), n = 1 ~ 5), was synthesized and studied for physicochemical properties and oral antitumor activity. Lipophilicity and aqueous solubility of the title complexes were greatly dependent on the alkyl chain length of the carboxylate ligand, and their partition coefficient and solubility changed by 4 or 5 orders of magnitude from acetate to hexanoate complexes. On the other hand, the range of their cathodic reduction potential (-546 ~ -403 mV) depending on the chain length of the carboxylate ligand was relatively small. Among the title complexes, the tetrakis(propionato)platinum(IV) complex, [Pt(O2CC2H5)4(dach)], with appropriate lipophilicity (log P = 0.18) and aqueous solubility (14.6 mg/mL) was found to exhibit better oral antitumor activity than JM216 against the human ovarian tumor xenograft SKOV3 in nude mice.

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DO - 10.1021/jm9904250

M3 - Article

C2 - 10753477

AN - SCOPUS:0342748699

SN - 0022-2623

VL - 43

SP - 1409

EP - 1412

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 7

ER -

Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes

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