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1983 (1)
1981 (1)
1Author    PeterL. Gutierrez, Maria Konieczny, George SosnovskyRequires cookie*
 Title    In the Search for New Anticancer Drugs, II 1 Antitumor Activity, Toxicity and Electron Spin Resonance of Spin Labeled Thio-TEPA Derivatives  
 Abstract    The spin labeled analog of Thio-Tepa, l-oxyl-2,2,6,6-tetramethyl-4-piperidyl-N,N;N',N'-bis (ethylene)-phosphorodiamidothioate (SL-O-TT), which contains a nitroxyl free radical linked by an oxygen bridge to phosphorus, has antitumor properties against P388 murine leukemia (T/C = 242) and a higher therapeutic ratio (5.15) than its parent compound, Thio-TEPA (2.75). The drug is less toxic to P388 cells in culture as judged by the 3 H-thymidine uptake. On the basis of electron spin resonance spectroscopy using L1210 cells incubated with SL-O-TT, it is concluded that the drug is bound to cells in culture in such a way as to restrict the motion of the nitroxyl label. A second spin labeled analog, l-oxyl-2,2,6,6-tetramethyl-4-amino-piperidyl-N,N;N',N'-bis (ethylene)-phosphorodiamidothioate (SL-NH-TT), containing a nitroxyl label linked by a nitrogen bridge to phosphorus, first synthesized by Russian workers, was prepared by an improved procedure in 95% yield. In vivo results indicate that this analog has about the same therapeutic value (2.73) as Thio-TEPA (2.75), and that higher doses of this compound are required than those for both the O-bridged analog and Thio-TEPA to achieve maximum T/C values. 
  Reference    Z. Naturforsch. 36b, 1612—1617 (1981); received June 12 1981 
  Published    1981 
  Keywords    Anticancer, Drugs, Thio-TEPA 
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 TEI-XML for    default:Reihe_B/36/ZNB-1981-36b-1612.pdf 
 Identifier    ZNB-1981-36b-1612 
 Volume    36 
2Author    George Sosnovsky, BuddhaD. PaulRequires cookie*
 Title    In the Search for New Anticancer Drugs, VI+ Structural Modifications of Cyclophosphamide  
 Abstract    Taking into consideration the known mechanism of the drug action of cyclophosphamide (1), several analogs and related compounds o, 6, 7, 9, 11, 12 and 27 were synthesized, and tested against lymphocytic leukemia P 388 in mice. CH °N P(0)NM2 (P(0)NM2 F /P(0)NM2 F ,P(0)NM2 I H3cV N 'H h>\ H CH 3 3 CH3 3 CH3 M=CH2CH2CI 5 6 7 (>™2 HO<3-P,O,NM2 / \ R HiC ' w o ' P-NCHUCHUCL 9 11, R = CI 12 27, r^nhch2CH2CH3 Moderate to high activity was found with 5 (T/C X 100 = 243 at a dose of 300 mg/kg), 7 (T/C x 100 = 173 at a dose of 10 mg/kg), 9 (T/C X 100 = 248 at a dose of 100 mg/kg) and 11 (T/C X 100 = 155 at a dose of 55 mg/kg). None of these compounds was found to be more active than 1 (T/C X 100 = 339 at a dose of 65 mg/kg). Although the essential position C4 for the enzymatic activation is completely blocked in 5, the compound posses-ses a high degree of activity. This result justifies a reevaluation of the proposed mechanism of drug action of 1 and its analogs. 
  Reference    Z. Naturforsch. 38b, 1146—1155 (1983); received August 30/December 24 1982 
  Published    1983 
  Keywords    Cyclophosphamide, Drugs, Anticancer, Synthesis, Leukemia P 388 
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 TEI-XML for    default:Reihe_B/38/ZNB-1983-38b-1146.pdf 
 Identifier    ZNB-1983-38b-1146 
 Volume    38