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Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1990 Jun; Vol. 33 (6), pp. 1721-8. - Publication Year :
- 1990
-
Abstract
- A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Humans
Leukemia L1210 drug therapy
Mice
Microtubules drug effects
Quinazolines chemical synthesis
Structure-Activity Relationship
Styrenes chemical synthesis
Tumor Cells, Cultured drug effects
Antineoplastic Agents pharmacology
Quinazolines pharmacology
Styrenes pharmacology
Tubulin
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 33
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 2088342
- Full Text :
- https://doi.org/10.1021/jm00168a029