The antitumor activity of di-n-butyltin(IV) glycylglycinate, and the correlation with the structure of dialkyltin(IV) glycylglycinates in solution studied by conductivity measurements and by infrared, nuclear magnetic resonance, and Mössbauer spectroscopic methods.
The in vivo activity of Bu2nSnGlyGly, Na(Cl2GaGlyGly), and ClGaGlyGly (GlyGly2- = glycylglycinate) has been investigated in connection with a number of tumors. Positive results have been obtained only for the Bu2nSnIV complex in the case of leukemia P-388. In order to try to interpret the pharmacological data on a molecular basis, the nature of the species present in solutions of AlK2Sn GlyGly complexes, as well as the reactivity of aqueous Me2SnGlyGly, have been studied. The presence of chelated species (I), Figure 1, in organic solvents, and the equilibrium (I) in equilibrium (II), Figure 1, in water and mixed water-organic solvent systems, have been inferred from conductance measurements, as well as from studies by Mössbauer (in frozen solution), 1H, 13C, and 119Sn NMR, and ir spectroscopy. Moreover, solvated (II) would release AlK2SnIV moieties, as evidenced by the slow formation of (Me2SnO)n from aqueous Me2Sn GlyGly. The involvement of (I) and (II) in the transportation of these drugs across cell membranes is discussed.
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009947:Organotin Compounds / Q000627:therapeutic use*; D013055:Spectrophotometry, Infrared / Q000379:methods; D013057:Spectrum Analysis / Q000379:methods; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
D009947:Organotin Compounds; C047648:di-n-butyltin glycylglycinate