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

Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, David Rowley, Jiadong Sun, Zenat Adeeb Nagib, Keykavous Parang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1154-1158
Number of pages5
JournalTetrahedron Letters
Volume55
Issue number6
DOIs
StatePublished - Feb 5 2014
Externally publishedYes

Keywords

  • Acetyl indole
  • Antiproliferative agents
  • Indolyl carbonitriles
  • Microwave-assisted synthesis
  • Multicomponent reactions

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

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  • Cite this

    El-Sayed, N. S., Shirazi, A. N., El-Meligy, M. G., El-Ziaty, A. K., Rowley, D., Sun, J., Nagib, Z. A., & Parang, K. (2014). Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity. Tetrahedron Letters, 55(6), 1154-1158. https://doi.org/10.1016/j.tetlet.2013.12.081