Structural requirements for inducing cardiotoxicity by anthracycline antibiotics: studies with neonatal rat cardiac myocytes in culture.
Neonatal rat cardiac myocytes maintained in tissue culture were utilized to screen cardiotoxicity induced by a number of adriamycin and daunomycin analogs. Cell toxicity was assessed by leakage of cytoplasmic enzymes and was confirmed by electron microscopy. A number of modifications of structure of adriamycin and daunomycin markedly altered the incidence of toxicity caused by these drugs. Even though some of these structural alterations markedly altered lipid solubility or reactivity of quinone function, these changes did not always account for the differences in the toxicity induced by anthracycline analogs. The cardiomyocyte culture system used in this simple screening technique should be useful in the development of active anthracycline analog with least cardiotoxic potential.
Shirhatti
V
V
George
M
M
Chenery
R
R
Krishna
G
G
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D009279:Naphthacenes; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase