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 ... View Full Text


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Article Info

DATE

1986-06

AUTHORS

F. Wingen, H. Sterz, H. Blum, H. Möller, W. Pittermann, B. L. Pool, H. J. Sinn, H. Spring, D. Schmahl

ABSTRACT

The aim of this study was to investigate whether the newly synthesized bisphosphonic acidlinked N-Lost derivative BAD retains bone-seeking and cytostatic properties. The paper describes experiments on mutagenicity in vitro and on toxicity in vivo. BAD is characterized by very low mutagenic activity toward histidine auxotrophic Salmonella typhimurium strains. Cytotoxic effects were tested in rat osteosarcoma and in Walker carcinosarcoma 256B. The LD50 of i.v. injected BAD was 146 mg/kg. Acute toxicity is probably caused by calcium complexing of the bisphosphonate part of the molecule. Labeling experiments showed moderate accumulation in bone and osteosarcoma, as well as in lung metastases. BAD effected high tumor growth inhibition in osteosarcoma and Walker carcinosarcoma-bearing rats and marked prolongation of survival; histologic and radiographic examination revealed rapid calcification of osteosarcoma and lung metastases. BAD-pretreatment produced protective effects against osteolysis induced by intratibially implanted Walker carcinosarcoma ascites cells. The cytostatic efficacy of equitoxic doses of BAD in rat osteosarcoma is comparable to that of dacarbazine and in Walker carcinosarcoma to that of melphalan. More... »

PAGES

209-219

References to SciGraph publications

  • 1974-12. The effect of two diphosphonates on the handling of calcium by rat kidney mitochondriain vitro in CALCIFIED TISSUE RESEARCH
  • 1982-12. Uptake and localization of99mTc-methylene diphosphonate in mouse osteosarcoma in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 1974-03. Effects of calcium on warm and cold receptors in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1980-05. Bone tumours induced in rats with radioactive cerium in BRITISH JOURNAL OF CANCER
  • 1982-11. Diphosphonate bone scanning agents — Current concepts in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 1981-08. The effect of diphosphonates on periosteal and bone cells in culture in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 1980-12. Influence of a diphosphonate on the cellular aspect of young bone tissue in CALCIFIED TISSUE INTERNATIONAL
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf00389236

    DOI

    http://dx.doi.org/10.1007/bf00389236

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033663353

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/3525574


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    83 melphalan
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    94 properties
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    97 rapid calcification
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