Synthesis and biological activities of topoisomerase I inhibitors, 6-arylmethylamino analogues of edotecarin.

Abstract

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.

• Authors: Satoshi Sunami, Teruyuki Nishimura, Ikuko Nishimura, Satoru Ito, Hiroharu Arakawa, Mitsuru Ohkubo
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 10 Pg. 3225-37 (May 28 2009) ISSN: 1520-4804 [Electronic] United States
• PMID: 19397324 (Publication Type: Journal Article)

Chemical References

• Amines
• Antineoplastic Agents
• Carbazoles
• Enzyme Inhibitors
• Hydrocarbons, Aromatic
• Pyridines
• Topoisomerase I Inhibitors
• edotecarin

Topics

• Amines (chemistry)
• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Carbazoles (chemistry)
• Cell Line, Tumor
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Female
• Humans
• Hydrocarbons, Aromatic (chemistry)
• Mice
• Pyridines (chemistry)
• Stomach Neoplasms (drug therapy, pathology)
• Structure-Activity Relationship
• Topoisomerase I Inhibitors
• Xenograft Model Antitumor Assays