Tumor inhibitors. 124. Structural requirements for antileukemic activity among the naturally occurring and semisynthetic maytansinoids

Autor:	S. M. Kupchan, L I Rebhun, Albert T. Sneden, G. A. Howie, R W Wang, Alan R. Branfman, W E McIvor, T C Schnaitman
Rok vydání:	1978
Předmět:	biology Ether Biological activity medicine.disease Leukemia chemistry.chemical_compound Maytansinol Biochemistry chemistry biology.animal Drug Discovery medicine Molecular Medicine Structure–activity relationship Cytotoxic T cell Sea urchin
Zdroj:	Journal of Medicinal Chemistry. 21:31-37
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm00199a006
Popis:	In an effort to determine the structural requirements for the significant antileukemic, cytotoxic, antitubulin, and antimitotic activity exhibited by the novel ansa macrolide, maytansine (1), four new C-3 ester and six new C-9 ether homologues were synthesized. The biological activities of these compounds were assayed and compared to the activities of previously reported, naturally occurring maytansinoids. From the data, it is apparent that presence of the C-3 ester is necessary for significant activity, and variations in the ester group are not accompanied by marked changes in activity. However, elimination of the ester group, as in maytansinol (7), maysine (8), normaysine (9), and maysenine (10), results in a significant decrease in biological activity. Blockage of the C-9 carbinolamide via etherification markedly reduces antileukemic and cytotoxic activity and slightly reduces antitubulin activity but has relatively little effect on antimitotic activity against sea urchin eggs. Thus, a free carbinolamide at C-9 is advantageous for optimal activity.
Databáze:	OpenAIRE
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