Structure-activity requirements for flavone cytotoxicity and binding to tubulin.

Abstract

A series of 79 flavones related to centaureidin (3,6,4'-trimethoxy-5, 7,3'-trihydroxyflavone, 1) was screened for cytotoxicity in the NCI in vitro 60-cell line human tumor screen. The resulting cytotoxicity profiles of these flavones were compared for degree of similarity to the profile of 1. Selected compounds were further evaluated with in vitro assays of tubulin polymerization and [3H]colchicine binding to tubulin. Maximum potencies for tubulin interaction and production of differential cytotoxicity profiles characteristic of 1 were observed only with compounds containing hydroxyl substituents at C-3' and C-5 and methoxyl groups at C-3 and C-4'.

• Authors: J A Beutler, E Hamel, A J Vlietinck, A Haemers, P Rajan, J N Roitman, J H Cardellina 2nd, M R Boyd
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 41 Issue 13 Pg. 2333-8 (Jun 18 1998) ISSN: 0022-2623 [Print] United States
• PMID: 9632366 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Biopolymers
• Flavonoids
• Tubulin
• centaureidin
• Colchicine

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Biopolymers
• Cell Survival (drug effects)
• Colchicine (metabolism)
• Drug Screening Assays, Antitumor
• Flavonoids (pharmacology)
• Humans
• Protein Binding (drug effects)
• Structure-Activity Relationship
• Tubulin (chemistry, metabolism)
• Tumor Cells, Cultured