Synthesis and Biological Activities of Topoisomerase I Inhibitors, 6-Arylmethylamino Analogues of Edotecarin

The replacement of 1,3-dihydroxy-2-propylamino moiety at the N6-position of edotecarin (1) by arylmethylamino groups yielded a number of more potent topoisomerase I inhibitors with better cytotoxic (CTX) activities in vitro than edotecarin. Among them, the three most potent pyridylmethyl analogues,...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2009-05, Vol.52 (10), p.3225-3237
Main Authors: Sunami, Satoshi, Nishimura, Teruyuki, Nishimura, Ikuko, Ito, Satoru, Arakawa, Hiroharu, Ohkubo, Mitsuru
Format: Article
Language:English
Subjects:
Amines - chemistry
Animals
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Biological and medical sciences
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Carbazoles - chemistry
Cell Line, Tumor
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
Female
General aspects
Humans
Hydrocarbons, Aromatic - chemistry
Medical sciences
Mice
Pharmacology. Drug treatments
Pyridines - chemistry
Stomach Neoplasms - drug therapy
Stomach Neoplasms - pathology
Structure-Activity Relationship
Topoisomerase I Inhibitors
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The replacement of 1,3-dihydroxy-2-propylamino moiety at the N6-position of edotecarin (1) by arylmethylamino groups yielded a number of more potent topoisomerase I inhibitors with better cytotoxic (CTX) activities in vitro than edotecarin. Among them, the three most potent pyridylmethyl analogues, compounds 22g, 22m, and 23c, showed better antitumor activities against MKN-45 human stomach cancer or MX-1 human breast cancer xenografted mice than those of edotecarin. Furthermore, compounds 22m and 23c exhibited complete response against MX-1 cells implanted in mice.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm801641t