6284-92-0Relevant articles and documents
Synthesis and Biochemical Evaluation of 3-Phenoxy-1,4-diarylazetidin-2-ones as Tubulin-Targeting Antitumor Agents
Greene, Thomas F.,Wang, Shu,Greene, Lisa M.,Nathwani, Seema M.,Pollock, Jade K.,Malebari, Azizah M.,McCabe, Thomas,Twamley, Brendan,OBoyle, Niamh M.,Zisterer, Daniela M.,Meegan, Mary J.
, p. 90 - 113 (2016/01/29)
Structure-activity relationships for a series of 3-phenoxy-1,4-diarylazetidin-2-ones were investigated, leading to the discovery of a number of potent antiproliferative compounds, including trans-4-(3-hydroxy-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (78b) and trans-4-(3-amino-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (90b). X-ray crystallography studies indicate the potential importance of the torsional angle between the 1-phenyl A ring and 4-phenyl B ring for potent antiproliferative activity and that a trans configuration between the 3-phenoxy and 4-phenyl rings is generally optimal. These compounds displayed IC50 values of 38 and 19 nM, respectively, in MCF-7 breast cancer cells, inhibited the polymerization of isolated tubulin in vitro, disrupted the microtubular structure in MCF-7 cells as visualized by confocal microscopy, and caused G2/M arrest and apoptosis. Compound 90b possessed a mean GI50 value of 22 nM in the NCI60 cell line screen, displayed minimal cytotoxicity, and was shown to interact at the colchicine-binding site on β-tubulin. Phosphate and amino acid prodrugs of both 78b and 90b were synthesized, of which the alanine amide 102b retained potency and is a promising candidate for further clinical development.
Synthesis and biological evaluation of arylcinnamide linked combretastatin-A4 hybrids as tubulin polymerization inhibitors and apoptosis inducing agents
Kamal, Ahmed,Bajee, Shaik,Lakshma Nayak, Vadithe,Venkata Subba Rao, Ayinampudi,Nagaraju, Burri,Ratna Reddy, Challa,Jeevak Sopanrao, Kapure,Alarifi, Abdullah
supporting information, p. 2957 - 2964 (2016/06/06)
A series of new molecules have been designed based on a hybridization approach by combining the arylcinnamide and combretastatin pharmacophores. These were synthesized and evaluated for their cytotoxic activity, effect on inhibition of tubulin polymerization and apoptosis inducing ability. Most of the conjugates exhibited significant cytotoxic activity against some representative human cancer cell lines and two of the conjugates 6i and 6p displayed potent cytotoxicity with GI50 values of 56 nM and 31 nM respectively against the human breast cancer cell line (MCF-7). SAR studies revealed that 3,4-substitution on the phenyl ring of the cinnamide moiety is beneficial for enhanced cytotoxicity. Moreover, G2/M cell cycle arrest was induced by these conjugates (6i and 6p) apart from tubulin polymerization inhibition (IC50 of 1.97 μM and 1.05 μM respectively). Further, mitochondrial membrane potential, Annexin V-FITC and caspase-9 activation assays suggested that these conjugates induce cell death by apoptosis. Docking studies revealed that these conjugates interact and bind at the colchicine binding site of the tubulin.
COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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Paragraph 0174; 0175, (2015/05/05)
The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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Paragraph 0232; 0233, (2015/06/24)
The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
Design and Synthesis of Aminostilbene-Arylpropenones as Tubulin Polymerization Inhibitors
Kamal, Ahmed,Kumar, G. Bharath,Polepalli, Sowjanya,Shaik, Anver Basha,Reddy, Vangala Santhosh,Reddy, M. Kashi,Reddy, Ch. Ratna,Mahesh, Rasala,Kapure, Jeevak Sopanrao,Jain, Nishant
, p. 2565 - 2579 (2015/08/24)
A series of aminostilbene - arylpropenones were designed and synthesized by Michael addition and were investigated for their cytotoxic activity against various human cancer cell lines. Some of the investigated compounds exhibited significant antiproliferative activity against a panel of 60 human cancer cell lines of the US National Cancer Institute, with 50% growth inhibition (GI50) values in the range from 50 value of 50) values ranging from 0.011 to 8.56μM. A cell cycle assay revealed that these compounds arrested the G2/M phase of the cell cycle. Two compounds exhibited strong inhibitory effects on tubulin assembly with IC50 values of 0.71 and 0.79μM. Moreover, dot-blot analysis of cyclinB1 demonstrated that some of the congeners strongly induced cyclinB1 protein levels. Molecular docking studies indicated that these compounds occupy the colchicine binding site of tubulin.
Synthesis and antitumor activity of feruloyl and caffeoyl derivatives This paper is dedicated to Prof. Wei-xiao Hu for his lifelong commitment to mentoring graduate students
Chen, Hui-Zhen,Chen, You-Bao,Lv, Ya-Ping,Zeng, Fang,Zhang, Juan,Zhou, Yong-Lie,Li, Han-Bing,Chen, Li-Fei,Zhou, Bin-Jie,Gao, Jian-Rong,Xia, Chun-Nian
supporting information, p. 4367 - 4371 (2015/02/06)
We developed two efficient protocols for the synthesis of feruloyl and caffeoyl derivatives from commercial vanillin and veratraldehyde. Pharmacological activities were assessed against a panel of human cancer cell lines in vitro. Most synthesized compounds demonstrated attractive cytotoxicity. Several new compounds demonstrated significant antiproliferative and cytotoxic activities against HeLa and Bewo tumor cell lines. In particular, 5-nitro caffeic adamantyl ester showed broad spectrum of tumor inhibition in 10 cell lines, and reduced tumor weight by 36.7% in vivo when administered at a dose of 40 mg kg-1.
Fluorinated cannabinoid CB2 receptor ligands: Synthesis and in vitro binding characteristics of 2-oxoquinoline derivatives
Turkman, Nashaat,Shavrin, Aleksander,Ivanov, Roman A.,Rabinovich, Brian,Volgin, Andrei,Gelovani, Juri G.,Alauddin, Mian M.
supporting information; experimental part, p. 5698 - 5707 (2011/10/13)
Cannabinoid receptor 2 (CB2) plays an important role in human physiology and the pathophysiology of different diseases, including neuroinflammation, neurodegeneration, and cancer. Several classes of CB2 receptor ligands, including 2-oxoquinoline derivatives, have been previously reported. We report the synthesis and results of in vitro receptor binding of a focused library of new fluorinated 2-oxoquinoline CB2 ligands. Twelve compounds, 13-16 18, 19, 21-24, 27, and 28 were synthesized in good yields in multiple steps. Human U87 glioma cells expressing either hCB1 (control) or hCB2 were generated via lentiviral transduction. In vitro competitive binding assay was performed using [3H]CP-55,940 in U87hCB1 and U87hCB2 cells. Inhibition constant (Ki) values of compounds 13-16, 18, 19, 21-24, 27, and 28 for CB2 were >10,000, 2.8, 5.0, 2.4, 22, 0.8, 1.4, >10,000, 486, 58, 620, and 2400 nM, respectively, and those for CB1 were >10,000 nM. Preliminary in vitro results suggest that six of these compounds may be useful for therapy of neuropathic pain, neuroinflammatory diseases and immune disorders. In addition, compound 19, with its subnanomolar Ki value, could be radiolabeled with 18F and explored for PET imaging of CB2 expression.
Synthesis and in vitro biological evaluation of carbon-11-labeled quinoline derivatives as new candidate PET radioligands for cannabinoid CB2 receptor imaging
Gao, Mingzhang,Wang, Min,Miller, Kathy D.,Hutchins, Gary D.,Zheng, Qi-Huang
experimental part, p. 2099 - 2106 (2010/06/12)
Cannabinoids have been recently proposed as a new family of potential antitumor agents, and cannabinoid receptor 2 (CB2) is believed to be over-expressed in tumor cells. This study was designed to develop new radioligands for imaging of CB2 receptor in ca
Synthesis and evaluation of 3-aroylindoles as anticancer agents: Metabolite approach
Wu, Yu-Shan,Coumar, Mohane Selvaraj,Chang, Jang-Yang,Sun, Hsu-Yi,Kuo, Fu-Ming,Kuo, Ching-Chuan,Chen, Ying-Jun,Chang, Chi-Yen,Hsiao, Chia-Ling,Liou, Jing-Ping,Chen, Ching-Ping,Yao, Hsien-Tsung,Chiang, Yi-Kun,Tan, Uan-Kang,Chen, Chiung-Tong,Chu, Chang-Ying,Wu, Su-Ying,Yeh, Teng-Kuang,Lin, Chin-Yu,Hsieh, Hsing-Pang
scheme or table, p. 4941 - 4945 (2010/03/02)
BPR0L075 (2) is a potential anticancer drug candidate designed from Combretastatin A-4 (1) based on the bioisosterismprinciple.Metabolites of 2, proposed from in vitrohumanmicrosome studies,were synthesized, leading to the identification of metabolite-der
Synthesis and biological evaluation of new disubstituted analogues of 6-methoxy-3-(3′,4′,5′-trimethoxybenzoyl)-1H-indole (BPR0L075), as potential antivascular agents
Ty, Nancy,Dupeyre, Gregory,Chabot, Guy G.,Seguin, Johanne,Tillequin, Francois,Scherman, Daniel,Michel, Sylvie,Cachet, Xavier
, p. 7494 - 7503 (2008/12/23)
6-Methoxy-3-(3′,4′,5′-trimethoxybenzoyl)-1H-indole (BPR0L075) (1) is a potent inhibitor of tubulin polymerization which exhibits both in vitro and in vivo activities against a broad spectrum of solid tumors. This compound was designed as a heterocyclic an
