- Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors
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A series of novel indole-based oxalamide and aminoacetamide derivatives were designed, synthesized, and evaluated for antiproliferative activities. Preliminary results revealed that compound 8g exhibited significant antiproliferative effect against PC-3,
- Chen, Peng,Diao, Peng-Cheng,Huang, Chuan,Huang, Jie Chun,Jian, Xie-Er,Li, Jun-Sheng,Yin, Jie,Zhao, Pei-Liang
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- Synthesis, biological evaluation, and molecular docking investigation of 3-amidoindoles as potent tubulin polymerization inhibitors
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A series of novel 3-amidoindole derivatives possessing 3,4,5-trimethoxylphenyl groups were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Some of them demonstrated moderate to potent activities in vitro against six cancer cell lines including MCF-7, MDA-MB-231, BT549, T47D, MDA-MB-468, and HS578T. The most active compound 27 inhibited the growth of T47D, BT549, and MDA-MB-231 cell lines with IC50 values at 0.04, 3.17, and 6.43 μM, respectively. Moreover, the flow cytometric analysis clearly revealed that compound 27 significantly inhibited growth of breast cancer cells through arresting cell cycle in G2/M phase via a concentration-dependent manner. In addition, the compound also exhibited the most potent anti-tubulin activity with IC50 values of 9.5 μM, which was remarkable, compared to CA-4. Furthermore, molecular docking analysis demonstrated the interaction of the compound 27 at the colchicine-binding site of tubulin. These preliminary results suggest that compound 27 is a very promising tubulin-binding agent and is worthy of further investigation aiming to the development of new potential anticancer agents.
- Chen, Peng,Zhuang, Yu-Xin,Diao, Peng-Cheng,Yang, Fang,Wu, Shao-Yu,Lv, Lin,You, Wen-Wei,Zhao, Pei-Liang
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p. 525 - 533
(2018/11/26)
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- Synthesis and biological evaluation of novel indole-pyrimidine hybrids bearing morpholine and thiomorpholine moieties
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Based on our previous screening hit compound 1, a series of novel indole-pyrimidine hybrids possessing morpholine or thiomorpholine moiety were synthesized via an efficient one-pot multistep synthetic method. The antiproliferative activities of the synthesized compounds were evaluated in?vitro against four cancer cell lines including HeLa, MDA-MB-231, MCF-7, and HCT116. The results revealed that most compounds possessed moderate to excellent potency. The IC50 values of the most promising compound 15 are 0.29, 4.04, and 9.48?μM against MCF-7, HeLa, and HCT116?cell lines, respectively, which are 48.0, 4.9, and 1.8 folds more active than the lead compound 1. Moreover, fluorescence-activated cell sorting analysis revealed that compound 14 showing the highest activity against HeLa (IC50?=?2.51?μM) displayed a significant effect on G2/M cell-cycle arrest in a concentration-dependent manner in HeLa cell line. In addition, representative nine active hybrids were evaluated for tubulin polymerization inhibitory activities, and compound 15 exhibited the most potent anti-tubulin activity showing 42% inhibition at 10?μM. These preliminary results encourage a further investigation on indole-pyrimidine hybrids for the development of potent anticancer agents that inhibit tubulin polymerization.
- Diao, Peng-Cheng,Li, Qiu,Hu, Meng-Jin,Ma, Yu-Feng,You, Wen-Wei,Hong, Kwon Ho,Zhao, Pei-Liang
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p. 110 - 118
(2017/04/13)
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- Expedient one-pot synthesis of indolo[3,2-c]isoquinolines via a base-promoted N-Alkylation/tandem cyclization
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A transition metal-free, one-pot protocol has been developed for the synthesis of 11H-indolo[3,2-c]isoquinolin-5-amines via the atom economical annulation of ethyl (2-cyano-phenyl)carbamates and 2-cyanobenzyl bromides. This method proceeds via sequential
- Nguyen, Huy H.,Fettinger, James C.,Haddadin, Makhluf J.,Kurth, Mark J.
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supporting information
p. 5429 - 5433
(2015/09/15)
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- Synthesis of the new ring system pyrrolizino[2,3-b]indol-4(5H)-one
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Derivatives of the new ring system pyrrolizino[2,3-b]indol-4(5H)-one were prepared in four steps starting from substituted benzonitriles bearing a functionalized amino group in the adjacent position. The unsubstituted- and the dimethoxy-pyrrolizinoindolon
- Diana, Patrizia,Stagno, Antonina,Barraja, Paola,Montalbano, Alessandra,Carbone, Anna,Parrino, Barbara,Cirrincione, Girolamo
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body text
p. 3374 - 3379
(2011/06/11)
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- Synthesis and biological evaluation of 1-methyl-2-(3′,4′, 5′-trimethoxybenzoyl)-3-aminoindoles as a new class of antimitotic agents and tubulin inhibitors
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The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent antiproliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.
- Romagnoli, Romeo,Baraldi, Pier Giovanni,Sarkar, Taradas,Carrion, Maria Dora,Cara, Carlota Lopez,Cruz-Lopez, Olga,Preti, Delia,Tabrizi, Mojgan Aghazadeh,Tolomeo, Manlio,Grimaudo, Stefania,Di Cristina, Antonella,Zonta, Nicola,Balzarini, Jan,Brancale, Andrea,Hsieh, Hsing-Pang,Hamel, Ernest
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p. 1464 - 1468
(2008/09/20)
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- Indole compounds as COX-2 inhibitors
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This invention provides a compound of the following formula: and the pharmaceutically acceptable salts thereof, wherein L is oxygen or sulfur; Y is a direct bond or C1-4alkylidene; Q is C1-6alkyl, C3-7cycloalkyl, phenyl, naphthyl, heteroaryl or the like; R1is hydrogen, C1-6alkyl or the like; R2is hydrogen, C1-4alkyl, C(O)R5wherein R5is C1-22alkyl or C2-22alkenyl, halosubstituted C1-8alkyl, halosubstituted C2-8alkenyl, —Y—C3-7cycloalkyl, —Y—C3-7cycloalkenyl, phenyl, naphthyl, heteroaryl or the like; X is halo, C1-4alkyl, hydroxy, C1-4alkoxy or the like; and n is 0, 1, 2 or 3, with the proviso that a group of formula —Y—Q is not methyl or ethyl when X is hydrogen; L is oxygen; R1is hydrogen; and R2is acetyl. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.
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