By Alan C. Sartorelli (Eds.)

ISBN-10: 0841203105

ISBN-13: 9780841203105

ISBN-10: 0841203369

ISBN-13: 9780841203365

content material: improvement of [alpha]-(N)-heterocyclic carboxaldehyde thiosemicarbazones with scientific strength as antineoplastic brokers / Alan C. Sartorelli and Krishna C. Agrawal --
Adriamycin / David W. Henry --
Biochemical pharmacology of the anthracycline antibiotics / Nicholas R. Bachur --
power bioreductive alkylating brokers / Ai Jeng Lin, Lucille A. Cosby, and Alan C. Sartorelli --
A evaluate of stories at the mechanism of motion of nitrosoureas / Glynn P. Wheeler.

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T h i s tumor i s i n t r i n s i c a l l y much l e s s s e n s i t i v e to a n t h r a c y c l i n e s and t h i s i s shown by the low s u r v i v a l time i n c r e a s e of Table V. 0 50 42 > 400 0/7 5/7 a Schedule: QD1-4, i p . Data from r e f . 109. 42% and l a c k of long-term s u r v i v o r s given by adriamycin. In c o n t r a s t AD32 gave f i v e out of seven 60-day s u r v i v o r s , an imp r e s s i v e r e s u l t as long-term s u r v i v o r s w i t h any a n t h r a c y c l i n e a r e not common i n the L1210 system.

Spectrophotometric DNA-binding s t u d i e s determined that compounds 47 and 48 had b i n d i n g constants s l i g h t l y greater than adriamycin but that the number of receptor s i t e s on the DNA was reduced by 25-50%. Compound 49 possessed a b i n d i n g constant about one-half that of adriamycin^but the apparent number of receptor s i t e s was e q u i v a l e n t to the a n t i b i o t i c . No b i o l o g i c a l data on these compounds have been published but i t i s s i g n i f i c a n t that such r e l a t i v e l y a c c e s s i b l e and simple analogs e x h i b i t DNA b i n d i n g c h a r a c t e r i s t i c s very s i m i l a r t o those of the much more complex parent a n t i b i o t i c s .

Although the i n v i v o a c t i v i t y of 38 i s unremarkable compared to adriamycin and daunomycin i t r e i n f o r c e s the c o n c l u s i o n suggested p r e v i o u s l y by the p r o p e r t i e nothing i r r e p l a c e a b l e i simply be a c a r r i e r f o r a potency-enhancing ammonium moiety. T h i s point w i l l be considered f u r t h e r i n f o l l o w i n g d i s c u s s i o n s . Several e s t e r s of daunomycinone analogous to 38 but derived from amine-bearing cyclohexane c a r b o x y l i c a c i d s have been patented and claimed as e f f e c t i v e against L1210 lymphocytic leukemia i n the mouse (123).

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Cancer Chemotherapy by Alan C. Sartorelli (Eds.)

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