Preparation, characterization, cytotoxicity, and mutagenicity of a pair of enantiomeric platinum(II) complexes with the potential to bind enantioselectively to DNA

Vickery, Kymberley; Bonin, Antonio M.; Fenton, Ronald R.; O’Mara, Shane M.; Russell, Pamela J.; Webster, Lorraine K.; Hambley, Trevor W.

doi:10.1021/jm00075a022

Cited by 44 publications

(38 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the isomers with R,R and S,S configurations at the asymmetric carbons produce the same type of intra-and interstrand cross-links (34), the biological activity of the two enantiomers is different, and the R,R enantiomer exhibits higher antitumor activity and lower mutagenicity than the S,S isomer (35). Chiral diamines other than 1,2-diaminocyclohexane have also been investigated (36)(37)(38)(39)(40).…”

Section: Chiral Discrimination In Platinum Anticancer Drugsmentioning

confidence: 99%

Chiral discrimination in platinum anticancer drugs.

Benedetti

Malina

Kašpárková

et al. 2002

Environ Health Perspect

View full text Add to dashboard Cite

In this article we review the biological activity of analogs of the antitumor drug cisplatin that contain chiral amine ligands. Interaction with DNA and formation of cross-links with adjacent purine bases are considered to be the crucial steps in the antitumor activity of this class of complexes. Because double-helical DNA has a chiral structure, interaction with enantiomeric complexes of platinum should lead to diastereomeric adducts. It has been demonstrated that DNA cross-links of platinum complexes with enantiomeric amine ligands not only can exhibit different conformational features but also can be processed differently by the cellular machinery as a consequence of these conformational differences. These results expand the general knowledge of how the stereochemistry of the platinum-DNA adduct can influence the cell response and contribute to understanding the processes that are crucial for antitumor activity. The steric requirements of the chiral ligands, in terms of configuration and flexibility, are also elucidated.

show abstract

Section: Chiral Discrimination In Platinum Anticancer Drugsmentioning

confidence: 99%

Chiral discrimination in platinum anticancer drugs.

Benedetti

Malina

Kašpárková

et al. 2002

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…The cytotoxicity of the compounds, evaluated on human breast cancer cell lines (MCF-7 and MDA-MB-231), was greatly influenced by the nature of the diamine ligand. The synthesis of a pair of enantiomeric Pt(II) complexes, [Pt(R,R-eap)Cl 2 ] and [Pt(S,S-eap)Cl 2 ] (eap = N,N-diethyl-2,4-pentanediamine) was described [90]. The in vitro cytotoxicity of each of the enantiomers toward murine leukemia and human bladder tumor cells has been measured.…”

Section: Diamine Platinum Complexesmentioning

confidence: 99%

Platinum Complexes as Anticancer Agents

Kostova

2006

PRA

444

206

View full text Add to dashboard Cite

The application of inorganic chemistry to medicine is a rapidly developing field, and novel therapeutic and diagnostic metal complexes are now having an impact on medical practice. Advances in biocoordination chemistry are crucial for improving the design of compounds to reduce toxic side effects and understand their mechanisms of action. Cisplatin, as one of the leading metal-based drugs, is widely used in the treatment of cancer. Significant side effects and drug resistance, however, have limited its clinical applications. Biological carriers conjugated to cisplatin analogs have improved specificity for tumor tissue, thereby reducing side effects and drug resistance. Platinum complexes with distinctively different DNA binding modes from that of cisplatin also exhibit promising pharmacological properties. This review focuses on recent advances in developing platinum anticancer agents with an emphasis on platinum coordination complexes.

show abstract

“…This hydrogen bridge is generally considered to be of importance for the interaction of platinum complexes with DNA [28] . In another model two H bonds are postulated, one to a phosphate O atom on the 5′ end of the GN7, GN7 Pt-chelate, the other one to the exocyclic O atom of the guanine on the 3′ end, the latter H bridge being the determinant in the adduct formation [29] .…”

Section: -----------------------------mentioning

confidence: 99%

[meso-1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]sulfato-platinum(II) — Pharmacokinetic Studies

Bernhardt¹,

Koch²,

Spruß³

et al. 1999

Arch. Pharm. Pharm. Med. Chem.

View full text Add to dashboard Cite

The maximally attainable level of the non‐plasma protein bound fraction of a single 10.0 μmol/kg i.p. dose of [meso‐1,2‐bis(2,6‐di‐chloro‐4‐hydroxyphenyl)ethylenediamine]sulfatoplatinum(II), a drug active on the murine, hormone‐sensitive MXT‐M‐3.2 breast cancer, lies markedly below the concentration causing a significant cytotoxic effect on a cell line derived from this tumor. This result confirms our opinion that the strong in vivo activity of this drug on hormone‐sensitive breast cancers is mediated by its estrogenic potency by analogy with high dosed steroidal and non‐steroidal estrogens. A specific cytotoxic effect utilizing the estrogen receptor as carrier, as formerly postulated, is unlikely.

show abstract

Preparation, characterization, cytotoxicity, and mutagenicity of a pair of enantiomeric platinum(II) complexes with the potential to bind enantioselectively to DNA

Cited by 44 publications

References 8 publications

Chiral discrimination in platinum anticancer drugs.

Chiral discrimination in platinum anticancer drugs.

Platinum Complexes as Anticancer Agents

[meso-1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]sulfato-platinum(II) — Pharmacokinetic Studies

Contact Info

Product

Resources

About