Structure-activity requirements for flavone cytotoxicity and binding to tubulin.
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'.
Beutler
J A
JA
Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Hamel
E
E
Vlietinck
A J
AJ
Haemers
A
A
Rajan
P
P
Roitman
J N
JN
Cardellina
J H
JH
Boyd
M R
MR
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001704:Biopolymers; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D001704:Biopolymers; D005419:Flavonoids; D014404:Tubulin; C083161:centaureidin; D003078:Colchicine