Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
J Med Chem ; 46(21): 4552-63, 2003 Oct 09.
Article in English | MEDLINE | ID: mdl-14521417

ABSTRACT

4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups. Thirty-five phenylhydrazone analogues of A-007 were synthesized and evaluated in vitro in a human primary cancer explant assay. Anticancer activities for selected analogues were also assayed for activity vs established human/murine cell lines. One-hundred-eighty-six fresh human solid tumors were used to screen for anticancer activity. Selected analogues were assayed for therapeutic indices (vs GM-CFC from bone marrow) in preparation for preclinical studies. Several polyaryl phenylhydrazones demonstrated improved cytotoxic activities by factors of 10(2)-10(3) when compared with A-007. However, the polyaryl quinone moieties of the latter analogues introduced potential toxic properties (cardiac, hematological) that do not exist with A-007.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Hydrazones/chemical synthesis , Hydrazones/pharmacology , Phenols/chemical synthesis , Phenols/pharmacology , Animals , Cell Division/drug effects , Crystallography, X-Ray , Culture Techniques , Drug Design , Drug Screening Assays, Antitumor , Humans , Hydrogen Bonding , Indicators and Reagents , Mice , Stem Cells/drug effects , Structure-Activity Relationship , Tumor Cells, Cultured
SELECTION OF CITATIONS
SEARCH DETAIL
...