Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity

被引：36
作者：
El-Sayed, Naglaa Salem [1 ,2 ]
Shirazi, Amir Nasrolahi [2 ,3 ]
El-Meligy, Magda Goda [1 ]
El-Ziaty, Ahmed Kamel [4 ]
Rowley, David [2 ]
Sun, Jiadong [2 ]
Nagib, Zenat Adeeb [1 ]
Parang, Keykavous [2 ,3 ]
机构：
[1] Natl Res Ctr, Cellulose & Paper Dept, Cairo 12622, Egypt
[2] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA
[3] Chapman Univ, Sch Pharm, Orange, CA 92866 USA
[4] Ain Shams Univ, Fac Sci, Dept Chem, Cairo 11566, Egypt
来源：
TETRAHEDRON LETTERS | 2014年 / 55卷 / 06期
关键词：
Antiproliferative agents; Acetyl indole; Indolyl carbonitriles; Microwave-assisted synthesis; Multicomponent reactions; MULTICOMPONENT REACTIONS; MICROWAVE IRRADIATION; BIOLOGICAL EVALUATION; PYRIDINE-DERIVATIVES; ANTITUMOR-ACTIVITY; ANTICANCER AGENTS; INDOLE ALKALOIDS; DRUG DISCOVERY; MARINE SPONGE; ANTIFUNGAL;
D O I：
10.1016/j.tetlet.2013.12.081
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
A novel class of 6-indolypyridine-3-carbonitrile derivatives were synthesized and evaluated for antiproliferative activities to establish structure-activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium acetate in the presence of piperidine as a catalyst, using a microwave irradiation method or a traditional thermal method. This was followed by chlorination for compounds 13a-e and subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C-2 position of the pyridine ring. The antiproliferative activity of these new nicotinonitriles was evaluated against human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix adenocarcinoma (HeLa) cells. Among all compounds, 2((2-aminoethyl)amino)-4-aryl-6-indolylnicotinonitriles series (15a, 15b, 15d, and 15e) exhibited higher antiproliferative activity on the three cancer cell lines with IC50 values of 4.1-13.4 mu M. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1154 / 1158
页数：5
相关论文
共 38 条
[1]   Design, synthesis and biological evaluation of novel pyridine derivatives as anticancer agents and phosphodiesterase 3 inhibitors [J].
Abadi, Ashraf H. ;
Ibrahim, Tamer M. ;
Abouzid, Khaled M. ;
Lehmann, Jochen ;
Tinsley, Heather N. ;
Gary, Bernard D. ;
Piazza, Gary A. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (16) :5974-5982
[2]   Cytotoxic bisindole alkaloids from a marine sponge Spongosorites sp. [J].
Bao, BQ ;
Sun, QS ;
Yao, XS ;
Hong, JK ;
Lee, CO ;
Sim, CJ ;
Im, KS ;
Jung, JH .
JOURNAL OF NATURAL PRODUCTS, 2005, 68 (05) :711-715
[3]   Microwave assisted combinatorial chemistry synthesis of substituted pyridines [J].
Cotterill, IC ;
Usyatinsky, AY ;
Arnold, JM ;
Clark, DS ;
Dordick, JS ;
Michels, PC ;
Khmelnitsky, YL .
TETRAHEDRON LETTERS, 1998, 39 (10) :1117-1120
[4]  
El-Zahor M. I., 1992, ALAZHAR B SCI, V3, P735
[5]   Synthesis, characterization of some benzazoles bearing pyridine moiety: Search for novel anticancer agents [J].
Elzahabi, Heba S. A. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (09) :4025-4034
[6]  
Feng J., 2009, SYNTHETIC COMMUN, V39, P1443
[7]   Indole alkaloids from the tunicate Aplidium meridianum [J].
Franco, LH ;
Joffé, EBD ;
Puricelli, L ;
Tatian, M ;
Seldes, AM ;
Palermo, JA .
JOURNAL OF NATURAL PRODUCTS, 1998, 61 (09) :1130-1132
[8]   Synthesis and evaluation of antifungal properties of a series of the novel 2-amino-5-oxo-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile and its analogues [J].
Gholap, Atul R. ;
Toti, Kiran S. ;
Shirazi, Fazal ;
Kumari, Ratna ;
Bhat, Manoj Kumar ;
Deshpande, Mukund V. ;
Srinivasan, Kumar V. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (21) :6705-6715
[9]   HAMACANTHIN-A AND HAMACANTHIN-B, NEW ANTIFUNGAL BIS INDOLE ALKALOIDS FROM THE DEEP-WATER MARINE SPONGE, HAMACANTHA SP [J].
GUNASEKERA, SP ;
MCCARTHY, PJ ;
KELLYBORGES, M .
JOURNAL OF NATURAL PRODUCTS, 1994, 57 (10) :1437-1441
[10]   New pyridone, thioxopyridine, pyrazolopyridine and pyridine derivatives that modulate inflammatory mediators in stimulated RAW 264.7 murine macrophage [J].
Hamdy, Nehal A. ;
Gamal-Eldeen, Amira M. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (11) :4547-4556
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