Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity |
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Authors: | Naglaa Salem El-Sayed Amir Nasrolahi Shirazi Magda Goda El-Meligy Ahmed Kamel El-Ziaty David Rowley Jiadong Sun Zenat Adeeb Nagib Keykavous Parang |
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Institution: | 1. Cellulose and Paper Department, National Research Center, Dokki, Cairo 12622, Egypt;2. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Kingston, RI 02881, United States;3. School of Pharmacy, Chapman University, Orange, CA 92866, United States;4. Chemistry Department, Faculty of Science Ain Shams University, Abbassia, Cairo 11566, Egypt |
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Abstract: | 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. |
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Keywords: | Antiproliferative agents Acetyl indole Indolyl carbonitriles Microwave-assisted synthesis Multicomponent reactions |
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