HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Antineoplastic activity, synergism, and antagonism of triarylalkylphosphonium salts and their combinations.

Abstract
Previously, some of us demonstrated that monocationic phosphonium salt [4-(formylphenyl)methyl]triphenylphosphonium chloride (A) and [4-(hydrazinocarboxy)-1-butyl]tris(4-dimethylaminophenyl)phosph oni um chloride (B) in combination, exhibit inhibitory synergism against ELA mammary carcinoma. Here we show that A + B also exhibits synergism against cultured MB49 murine bladder carcinoma, but antagonism against HT-29 human colon carcinoma. This is probably due to assembly of the hydrazone (C) in situ: synthetic C is a more potent growth inhibitor than either A or B for MB49 and ELA, yet inferior to B for HT-29 cells. A, B, C, [4-(hydrazinocarboxy)-1-butyl]tris(3-tolyl)phosphonium chloride (D) and [4-(methylcarboxy)butyl]triphenylphosphonium chloride (F) selectively inhibit carcinoma growth relative to untransformed cells, most likely due to high carcinoma transmembrane potentials. D and F are tolerated in mice at 100 mg/kg. Intraperitoneal administration of D slows subcutaneous HT-29 xenograft growth by 41 to 59% versus controls in nu/nu mice, and intraperitoneal administration of B slows MB49 xenograft growth by 46 to 57% versus controls and extends the median lifespan of mice bearing ELA breast carcinoma allografts by 86%. Triarylalkylphosphonium salts represent a promising class of antineoplastic cations exhibiting unusual selectivity and synergism.
AuthorsJ Patel, D Rideout, M R McCarthy, T Calogeropoulou, K S Wadwa, A R Oseroff
JournalAnticancer research (Anticancer Res) 1994 Jan-Feb Vol. 14 Issue 1A Pg. 21-8 ISSN: 0250-7005 [Print] GREECE
PMID8166451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Organophosphorus Compounds
Topics
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols (antagonists & inhibitors, pharmacology)
  • Cell Division (drug effects)
  • Cercopithecus aethiops
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Organophosphorus Compounds (antagonists & inhibitors, pharmacology)
  • Rats

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: