By Alan C. Sartorelli (Eds.)
content material: improvement of [alpha]-(N)-heterocyclic carboxaldehyde thiosemicarbazones with scientific capability 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 overview of stories at the mechanism of motion of nitrosoureas / Glynn P. Wheeler.
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Additional resources for Cancer Chemotherapy
A l t e r a t i o n of c e l l surface a r c h i t e c t u r e i s a new e f f e c t of adriamycin r e c e n t l y reported by Murphree et a l . (93). Using a new assay technique (94) they found that concanavalin A-induced a g g l u t i n a t i o n of S180 c e l l s was enhanced s e v e r a l f o l d f o l l o w i n g drug exposure. As the amount of l e c t i n bound was unchanged t h i s suggests that adriamycin a f f e c t s the c l u s t e r i n g of concanavalin A binding s i t e s . The p o s s i b i l i t y that adriamycin and daunomycin act by i n t e r ference with microtubule f u n c t i o n during m i t o s i s has been r a i s e d by the work of Dano (95,96).
In the f o l l o w i n g d i s c o u r s e the model w i l l be d i s c u s s e d i n terms of i t s a b i l i t y to r a t i o n a l i z e t e s t data among a n t h r a c y c l i n e d e r i v a t i v e s and analogs. Daunomycin and ^A^iamycin Dérivât The c a r b o n y l group at C-ÎT^oT^dajji^ selectively derivat i z e d by standard carbonyl reagents and, as would be expected, the amino group i s a l s o s e l e c t i v e l y attacked by a c y l a t i n g agents. For t h i s reason d e r i v a t i v e s on these f u n c t i o n a l groups r e c e i v e d e a r l y a t t e n t i o n i n s t r u c t u r e - a c t i v i t y s t u d i e s (51,98).
I t i s c l e a r that adriamycin and daunomycin have profound d e l e t e r i o u s e f f e c t s on n u c l e i c a c i d synthesis and t h i s property must be involved i n t h e i r mechanism of a c t i o n . However, not a l l DNA-related b i o l o g i c a l t h e s i s i n h i b i t i o n . Fo a n t i m i t o t i c e f f e c t s were evident i n c u l t u r e d mouse c e l l s at daunomycin l e v e l s much too low to a f f e c t n u c l e i c a c i d synthes i s (82). They a l s o demonstrated that the drug abruptly blocked m i t o s i s when given only a few minutes before prophase.