ABSTRACT
Racemic chlorobromofosfamide (CBM-4A) is a bromine substituted analog of ifosfamide. The studies reported here were aimed at establishing the general pharmacological properties and toxicologic profile of this compound. Acute and cumulative toxicity, behavioral screening tests and effects of subchronic and chronic treatment (influence on body weight, mortality, blood morphology, proteins level, urea and creatinine concentration, enzymes activity) were taken into account. Summarized data revealed that CBM-4A possessed similar properties as other oxazaphosphorine cytostatics.
Subject(s)
Antineoplastic Agents/pharmacology , Ifosfamide/analogs & derivatives , Animals , Antineoplastic Agents/toxicity , Blood Proteins/drug effects , Blood Proteins/metabolism , Body Temperature/drug effects , Body Weight/drug effects , Dose-Response Relationship, Drug , Hematocrit , Hemoglobins/drug effects , Hemoglobins/metabolism , Ifosfamide/pharmacology , Ifosfamide/toxicity , Lethal Dose 50 , Male , Mice , Rats , Rats, Wistar , StereoisomerismABSTRACT
The effect of two newly synthesized 5-amino modified analogues of rubidomycine was submitted to preliminary pharmacological and histological investigations in healthy Albino Swiss mice. The results showed a similarity of the tested properties of the new compounds and commercial rubidomycine, suggesting the same spectrum undesired side-effects after acute administration. Of the two novel compounds DR-22 was found to be less toxic, while much potent in its action on the haematopoietic system in comparison to rubidomycine, in prolonged treatment. DR-22 is a candidate for further, more detailed investigations.
Subject(s)
Daunorubicin/analogs & derivatives , Daunorubicin/pharmacology , Analgesics , Animals , Daunorubicin/toxicity , Female , Heart/drug effects , Hematopoietic System/drug effects , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Male , Mice , Motor Activity/drug effects , Myocardium/pathologyABSTRACT
In experiments carried out on Albino-Swiss mice we tried to compare some pharmacological properties of standard compound-rubidomycin with its 4 newly synthetized derivatives. DR-16 appeared to be more toxic compound than rubidomycin and DR-19 was found to possess the lowest toxicity.
Subject(s)
Daunorubicin/analogs & derivatives , Daunorubicin/toxicity , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Blood Proteins/analysis , Body Weight/drug effects , Male , Mice , Organ Size/drug effects , Structure-Activity RelationshipABSTRACT
Comparison of pharmacological properties of commercial racemic Cyclophosphamide and its D- and L-enantiomers was performed in experiments on mice and rats. Acute toxicity, behavioral screening tests and the effects of subchronic treatment (influence on body mass, the increase of the mass of internal organs, mortality, morphology of peripheral blood, biochemical investigations of blood plasma, microscopic evaluation of liver and bladder) were taken into account. Summarized results revealed the most pronounced toxicity of D-cyclophosphamide. L-enantiomer was more toxic when compared with racemate. As several reports in literature confirmed the greatest antineoplastic activity of L-form in animals, the suggestion of further clinical investigation of levorotatory form as a separate preparation has been put forward.
Subject(s)
Cyclophosphamide/analogs & derivatives , Cyclophosphamide/pharmacology , Liver/pathology , Motor Activity/drug effects , Animals , Blood Pressure/drug effects , Body Temperature/drug effects , Body Weight/drug effects , Cyclophosphamide/toxicity , Female , Heart Rate/drug effects , Lethal Dose 50 , Liver/drug effects , Male , Mice , Peristalsis/drug effects , Rats , Rats, Inbred Strains , Respiration/drug effects , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Some pharmacological properties of commercial racemic ifosfamide (Holoxan) and its D- and L-enantiomers were compared in experiments on mice and rats. Although values of acute toxicity and some results of subchronic treatment revealed better parameters of L-form in comparison to racemic mixture, distinct hepatotoxic effects and thrombocytopenia noted in the course of prolonged treatment seem to be the important factors limiting therapeutic usefulness of levorotatory form.
Subject(s)
Ifosfamide/analogs & derivatives , Ifosfamide/toxicity , Animals , Blood Pressure/drug effects , Body Temperature/drug effects , Body Weight/drug effects , Female , Heart Rate/drug effects , Ifosfamide/pharmacology , Mice , Motor Activity/drug effects , Organ Size/drug effects , Peristalsis/drug effects , Respiration/drug effects , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Comparison of pharmacological properties of commercial, racemic trofosfamide (Ixoten) and its dextrorotatory and levorotatory derivatives was performed in experiments on mice. Acute and cumulative toxicity, behavioral screening tests and effects of subchronic treatment (growth of body mass, mortality, blood morphology, proteins level, enzymes activity, microscopic evaluation of liver slices) were taken into account. Summarized data revealed more pronounced toxicity of enantiomers, particularly D-form, as compared with racemate.
