796072-79-2Relevant academic research and scientific papers
Synthesis and biological evaluation of indole-based, anti-cancer agents inspired by the vascular disrupting agent 2-(3′-hydroxy-4′- methoxyphenyl)-3-(3″,4″,5″-trimethoxybenzoyl)-6-methoxyindole (OXi8006)
MacDonough, Matthew T.,Strecker, Tracy E.,Hamel, Ernest,Hall, John J.,Chaplin, David J.,Trawick, Mary Lynn,Pinney, Kevin G.
, p. 6831 - 6843 (2013)
The discovery of a 2-aryl-3-aroyl indole-based small-molecule inhibitor of tubulin assembly (referred to as OXi8006) inspired the design, synthesis, and biological evaluation of a series of diversely functionalized analogues. In the majority of examples, the pendant 2-aryl ring contained a 3-hydroxy-4-methoxy substitution pattern, and the fused aryl ring featured a 6-methoxy group. Most of the variability was in the 3-aroyl moiety, which was modified to incorporate methoxy (33-36), nitro (25-27), halogen (28-29), trifluoromethyl (30), or trifluoromethoxy (31-32) functionalities. In two analogues (34 and 36), the methoxy substitution pattern in the fused aryl ring varied, while in another derivative (35) the phenolic moiety was translocated from the pendant 2-aryl ring to position-7 of the fused aryl ring. Each of the compounds were evaluated for their cytotoxicity (in vitro) against the SK-OV-3 (ovarian), NCI-H460 (lung), and DU-145 (prostate) human cancer cell lines and for their ability to inhibit tubulin assembly. Four of the compounds (30, 31, 35, 36) proved to be potent inhibitors of tubulin assembly (IC50 5 μM), and three of these compounds (31, 35, 36) were strongly cytotoxic against the three cancer cell lines. The most active compound (36) in this series, which incorporated a methoxy group at position-7, was comparable in terms of inhibition of tubulin assembly and cytotoxicity to the lead compound OXi8006.
Synthesis of a 2-aryl-3-aroyl indole salt (OXi8007) resembling combretastatin A-4 with application as a vascular disrupting agent
Hadimani, Mallinath B.,MacDonough, Matthew T.,Ghatak, Anjan,Strecker, Tracy E.,Lopez, Ramona,Sriram, Madhavi,Nguyen, Benson L.,Hall, John J.,Kessler, Raymond J.,Shirali, Anupama R.,Liu, Li,Garner, Charles M.,Pettit, George R.,Hamel, Ernest,Chaplin, David J.,Mason, Ralph P.,Trawick, Mary Lynn,Pinney, Kevin G.
, p. 1668 - 1678 (2013/10/22)
The natural products colchicine and combretastatin A-4 are potent inhibitors of tubulin assembly, and they have inspired the design and synthesis of a large number of small-molecule, potential anticancer agents. The indole-based molecular scaffold is prom
INDOLE-CONTAINING COMPOUNDS WITH ANTI-TUBULIN AND VASCULAR TARGETING ACTIVITY
-
Page 31, (2010/02/09)
Trimethoxyphenyl substituted indole ligands have been discovered which demonstrate impressive cytotoxicity as well as a remarkable ability to inhibit tubulin assembly. Such compounds as well as related derivatives are excellent clinical candidates for the
