ABSTRACT
The growth-inhibiting effect on the roots of maize and cucumber shoots was studied. We tested 53 triamine complexes of platinum (cis*- and trans*-[Pt(NH3)*2LCl]Cl, cis*- and trans*-[PtHx*2LCl]Cl and [PtenLCl]Cl, where Hx is hydroxylamine, en is ethylenediamine, and L are various heterocycles, which either have biological activity and occur in the cells or have no biological activity and are foreign to the cells). The cis*-[Pt(NH3)*2LCl]Cl and [PtenLCl]Cl complexes showed cytostatic properties, and the latter were effective at higher concentrations. Small changes in the composition of ligand L led to marked changes in the biological activity of the complexes. In order to characterize the effect of the complexes, we first determined the time of development of the lateral root from its initial appearance to its divergence from the main root (Tlat). The complexes with cytostatic properties markedly inhibited root branching and increased Tlat. The other complexes had virtually no effect on Tlat and reduced the zone of lateral roots only at the expense of inhibition of the main root growth. The complexes with cytostatic properties markedly inhibited the main root growth with time. Parallel studies conducted in the Oncological Research Center, Russian Academy of Medical Sciences have shown that the complexes with cytostatic properties display distinct antitumor activity.
Subject(s)
Organoplatinum Compounds/pharmacology , Cell Division/drug effects , Organoplatinum Compounds/chemistry , Plant Roots/cytology , Plant Roots/drug effects , Stereoisomerism , Structure-Activity RelationshipSubject(s)
Cisplatin/therapeutic use , Melphalan/therapeutic use , Neoplasms, Experimental/drug therapy , Animals , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drug Therapy, Combination , Melphalan/administration & dosage , Melphalan/adverse effects , Mice , Neoplasm Transplantation , Neoplasms, Experimental/immunologyABSTRACT
Therapeutic properties of cis-dichlorodiammineplatinum (II) were studied on 12 strains of transplantable tumors and leukemias in mice. The compound is characterized by a wide spectrum of antitumor action. The greatest effect was gained in adenocarcinoma of the lage intestine (strain AKATOL), proventricular cancer (strain PRG) and adenocarcinoma of the mammary gland (strain Ca-755). The terms of survival in mice with leukemia (strain La and L-1210) and ascites hepatoma 22 are increased considerably. In some L-1210 animals the complete cure was noted. Cis-dichlorodiammineplatinum (II) may be effectively combined with sarcolysin. Much greater antitumor effect was obtained on 3 tumor strains (AKATOL, Ca-755 and sarcoma 37) with the combined therapy than with each drug used separately. The histological study of Ca-755 during chemotherapy indicated that immunocompetent cells of the organism play an important role in the mechanism of antitumor action of the platinum complex. This is manifested in the development of intensive lymphohistiocytic reaction around and inside the tumor. A damage to the convoluted tubules of the kidney and intestinal villi is one of the main adverse side-effects of the combination.