title: Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity.
abstract: A novel class of 6-indolypyridine-3-carbonitrilile 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 compounds13a-eand subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C2position 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, and15e) exhibited higher antiproliferative activity cells with IC50values of 4.1-13.4 μM.
authors.affiliation: Cellulose and Paper Department, National Research Center, Dokki 12622, Cairo, Egypt ; Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States.
authors.forename: Naglaa Salem
authors.initials: NS
authors.lastname: El-Sayed
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States ; School of Pharmacy, Chapman University, Orange, CA, 92866, USA.
authors.forename: Amir Nasrolahi
authors.initials: AN
authors.lastname: Shirazi
authors.affiliation: Cellulose and Paper Department, National Research Center, Dokki 12622, Cairo, Egypt.
authors.forename: Magda Goda
authors.initials: MG
authors.lastname: El-Meligy
authors.affiliation: Chemistry Department, Faculty of Science Ain Shams University, Abbassia, Cairo, 11566, Egypt.
authors.forename: Ahmed Kamel
authors.initials: AK
authors.lastname: El-Ziaty
authors.affiliation: Cellulose and Paper Department, National Research Center, Dokki 12622, Cairo, Egypt.
authors.forename: Zenat Adeeb
authors.initials: ZA
authors.lastname: Nagib
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States ; School of Pharmacy, Chapman University, Orange, CA, 92866, USA.
authors.forename: Keykavous
authors.initials: K
authors.lastname: Parang
keywords: Antiproliferative agents; Indole; Indolyl carbonitriles; Microwave-assisted Synthesis; Multicomponent Reactions