- Synthesis, biological evaluation and mechanism study of chalcone analogues as novel anti-cancer agents
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A series of novel chalcone analogues were designed, synthesized and evaluated as anticancer agents. The results of antiproliferative activity tests showed that most of the analogues exhibited moderate to very good antiproliferative activities with GI50 values in the micromol to sub-micromol range. Especially compound 10a gave 0.026 μM to 0.035 μM GI50 for five cancer cell lines. The mechanistic studies including tubulin polymerization inhibition, disruption of microtubule dynamics and cell cycle arrest assay demonstrated that compound 10a could effectively inhibit in vitro cellular tubulin polymerization, interfere with the mitosis, resulting in a prolonged G2/M cell cycle arrest and ultimately lead to cell apoptosis of cancer cells. Taken together, these results suggested that 10a may became a promising lead compound for development of new anticancer drugs.
- Chen, Jie,Yan, Jun,Hu, Jinhui,Pang, Yanqing,Huang, Ling,Li, Xingshu
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p. 68128 - 68135
(2015/08/24)
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- Synthesis, biological evaluation and mechanism study of a class of benzylideneindanone derivatives as novel anticancer agents
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A series of new benzylideneindanone derivatives were designed, synthesized and evaluated as antitumor agents. Structure-activity relationship (SAR) studies showed that derivatives with 4,5,6-trimethoxyl on an indanone moiety displayed good anti-proliferative activities. Especially, compound 5a demonstrated the most potent inhibitory activity, with GI50 values from 0.172 to 0.57 μM for five kinds of cancer cell lines. Further investigation showed that 5a could inhibit microtubule polymerization and thus induce G2/M phase arrest and apoptosis in A549 cells. Our findings revealed the benzylideneindanone moiety as a new attractive scaffold for mitosis-targeting drug discovery.
- Hu, Jinhui,Yan, Jun,Chen, Jie,Pang, Yanqing,Huang, Ling,Li, Xingshu
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p. 1318 - 1327
(2015/07/15)
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- TUBULIN BINDING AGENTS
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The invention provides combretastatin A-4 like compounds that are modified to have enhanced tubulin binding activity and in some embodiments the ability to promote accumulation in the vasculature undergoing angiogenesis (homing activity). The compounds are based on the combretastatin A-4 skeletal structure having a tubulin-binding pharmacophore comprising two fused rings (A and B rings) in which the B ring is substituted with (a) an aromatic ring structure (C ring) and (b) a second substituent/functional group that comes off the B ring. The aromatic ring structure is typically a six membered ring phenolic or aniline structure, or may also be a fused ring structure such as a substituted or unsubstituted naphthalene. The second substituent on the B ring may for example be a substituent which has been found to provide enhanced tubulin binding activity (for example a carbonyl group), or may be a substituent that facilitates functionalisation of the B ring (for example an hydroxyl or amine group), or it may be a binding agent for a target that is preferentially expressed on vasculature undergoing angiogenesis, and not expressed on quiescent vasculature.
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- Efficient Method for Preparing Functionalized Benzosuberenes
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The disclosed process can efficiently synthesize functionalized benzosuberenes. The process provides an improved method of production of benzosuberene and compounds containing a benzosuberene moiety, which is characterized by a ring closing methodology comprising reaction of a 5-phenylpentanoic acid with Eaton's reagent to form the benzosuberone. The process, optionally, further includes steps for adding a functional group at the ketone position.
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Page/Page column 11-12
(2012/06/01)
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- Method of inhibiting sweetness
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The sweetness of an ingestible product containing a sweetening sugar or sugar alcohol in large quantities can be reduced by incorporating therein a sweetness-reducing amount of at least one compound of the general formula: STR1 in which m represents 0 or 1, and when m represents 0, n represents 1, 2 or 3, and p represents 1, 2, 3 or 4, and when m represents 1, n represents 1 or 2 and p represents 0, 1, 2, 3 or 4; the substituents R, which may be the same or different, each represent a lower alkoxy group, e.g. with 1 to 5 carbon atoms, phenoxy group or a lower alkyl or trifluoromethyl group; and/or two substituents R together represent an aliphatic chain linked to the phenyl ring at two positions, either directly or via an oxa-group, e.g. an alkylenedioxy, alkenylenedioxy, alkylenoxy or alkenylenoxy group; and/or one substituent R represents a hydroxy group while at least one other substituent R represents an alkoxy group; and X+ represents a physiologically acceptable cation.
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