TY - JOUR
T1 - Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity
AU - El-Sayed, Naglaa Salem
AU - Shirazi, Amir Nasrolahi
AU - El-Meligy, Magda Goda
AU - El-Ziaty, Ahmed Kamel
AU - Rowley, David
AU - Sun, Jiadong
AU - Nagib, Zenat Adeeb
AU - Parang, Keykavous
PY - 2014/2/5
Y1 - 2014/2/5
N2 - 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 C2 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 μM.
AB - 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 C2 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 μM.
KW - Acetyl indole
KW - Antiproliferative agents
KW - Indolyl carbonitriles
KW - Microwave-assisted synthesis
KW - Multicomponent reactions
UR - http://www.scopus.com/inward/record.url?scp=84895023421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895023421&partnerID=8YFLogxK
U2 - 10.1016/j.tetlet.2013.12.081
DO - 10.1016/j.tetlet.2013.12.081
M3 - Article
C2 - 24678129
AN - SCOPUS:84895023421
SN - 0040-4039
VL - 55
SP - 1154
EP - 1158
JO - Tetrahedron Letters
JF - Tetrahedron Letters
IS - 6
ER -