Anticancer-agent-linked phosphonates with antiosteolytic and antineoplastic properties: a promising perspective in the treatment of bone-related malignancies? View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1990-07

AUTHORS

T. Klenner, F. Wingen, B. K. Keppler, B. Krempien, D. SchmÄhl

ABSTRACT

Bisphosphonates are compounds with a high affinity for bone and other calcified tissues. They inhibit tumor-induced bone destruction and the associated hypercalcemia by hindering the activity of the osteoclasts. Owing to a long biological half-life of bisphosphonates in the bone, a treatment using a prophylactic regimen seems possible. This paper summarizes preclinical studies with the bisphosphonate 3-amino-1-hydroxypropylidene-1, 1-diphosphonic acid and two methyl derivatives; S-N,N-dimethylamino-1-hydroxypropylidene-1,1-diphosphonic acid and 4-N,N-dimetyhlamino-1-hydroxybutylidene-1, 1-diphosphonic acid with respect to their bone-protecting activity in therapy as well as in prophylaxis. To find substances that are useful for the treatment of primary tumor, as well as bone metastasis, we synthesized and testedcis-diammine[nitrilotris(methylphosphonato) (2-)-O1,N1]platinum(II) andcis-diammine{[bis-(phosphonatomethyl)amino]acetato(2-)-O1, N1} platinum(II), which contain both an osteotropic and an antineoplastic moiety. Experiments were carried out: (a) in the intratibial transplanted Walker carcinosarcoma 256B of the rat, which mimics osteolytic bone metastasis, and (b) in the transplantable osteosarcoma of the rat, which shows a histology and metastatic pattern similar to that found in man. These investigations indicate that it is possible to effect adjuvant therapy of bone metastases by combination of two compounds with different properties into one structure without losing the therapeutic characteristics of the parent compounds. They thus provide evidence that it may be possible to design compounds well suited for the therapeutic or prophylactic treatment of bone-related malignancies. More... »

PAGES

341-350

References to SciGraph publications

  • 1988-08-01. The value of bone marrow examination for tumor staging in breast cancer in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 1986-06. Synthesis, antitumor activity, distribution and toxicity of 4-[4-[Bis(2-chloroethyl)amino]phenyl]-1-hydroxybutane-1 1-bisphosphonic acid (BAD), a new lost derivative with increased accumulation in rat osteosarcoma in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 1986-11. Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat in CALCIFIED TISSUE INTERNATIONAL
  • 1986-07. Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate in CALCIFIED TISSUE INTERNATIONAL
  • 1985-05. Inhibition by aminohydroxypropylidene bisphosphonate (AHPrBP) of 1,25(OH)2 vitamin D3-induced stimulated bone turnover in the mouse in CALCIFIED TISSUE INTERNATIONAL
  • 1982-11. Diphosphonate bone scanning agents — Current concepts in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 1983-12. Apposition and resorption of bone during oral treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in CALCIFIED TISSUE INTERNATIONAL
  • 1986-02. Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 1987-12. 3(Amino-1,1-hydroxypropylidene) bisphosphonate (APD) for hypercalcaemia of breast cancer in BRITISH JOURNAL OF CANCER
  • 1987-01. Antimetastatic effects of razoxane in a rat osteosarcoma model in CLINICAL & EXPERIMENTAL METASTASIS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf01612916

    DOI

    http://dx.doi.org/10.1007/bf01612916

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1023638592

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/2152296


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