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[Development of antitumor platinum complexes].

Y Kidani

    Gan to Kagaku Ryoho. Cancer & Chemotherapy
    |December 1, 1983
    PubMed
    Summary
    This summary is machine-generated.

    Platinum (Pt) complexes, initially developed to treat various cancers, face challenges with toxicity and resistance. Research focuses on creating new Pt complexes, like those in clinical trials, to improve efficacy against solid tumors.

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    Biological & pharmaceutical bulletin·1993

    Area of Science:

    • Medicinal Chemistry
    • Coordination Chemistry
    • Oncology

    Background:

    • Discovery of cis-diamminedichloroplatinum(II) (DDP) in 1969 revealed significant antitumor activity.
    • DDP exhibits severe nephrotoxicity, nausea, vomiting, and ototoxicity, limiting its clinical application.
    • DDP is effective against bladder, testicular, ovarian, and head and neck cancers.

    Purpose of the Study:

    • To review the development of second-generation platinum (Pt) complexes aimed at reducing DDP's toxicity.
    • To discuss strategies for synthesizing novel Pt complexes with improved antitumor activity.
    • To explore the potential of Pt complexes against slow-growing solid tumors.

    Main Methods:

    • Modification of carrier ligands and leaving groups to attenuate nephrotoxicity.

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  • Development of combination therapies and hydration protocols to mitigate DDP side effects.
  • Synthesis and evaluation of new Pt complexes, including those in clinical trials (e.g., CBDCA, CHIP, l-OHP).

    • Main Results:

    • Changing ligands and leaving groups can reduce nephrotoxicity.
    • Certain Pt complexes (e.g., dach, 1,2-cycloheptanediamine Pt complexes) show no cross-resistance with DDP-resistant cell lines.
    • Second-generation Pt complexes are undergoing clinical trials for enhanced efficacy and reduced toxicity.

    Conclusions:

    • Ongoing research focuses on developing novel platinum complexes to overcome DDP's limitations.
    • Coordination chemistry plays a crucial role in designing Pt complexes effective against slow-growing solid tumors.
    • Future Pt complexes aim for improved therapeutic indices, targeting specific cancers with reduced side effects.