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 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 cells with IC50 values of 4.1–13.4 μM.

One‐Pot Synthesis of New Thiadiazolyl‐Pyridines as Anticancer and Antioxidant Agents

“…Moreover, an electron impact mass spectroscopic technique gave its correct molecular ion peak at m/z =370.4 (Experimental section). The reaction goes in parallel to literature .…”

Novel Polyfunctional Pyridines as Anticancer and Antioxidant Agents. Synthesis, Biological Evaluation and <i>in Silico</i> ADME-T Study

“…17) As far as the chemotherapeutic potential is concerned, pyridine derivatives have come into view as heterocycles with versatile antimicrobial, 18) antitubercular 19) and anticancer [20][21][22] activities. Most notably, several functionalized pyridinecarbonitriles have received much interest for their peculiar antineoplastic [23][24][25] as well as antioxidant 26,27) activities. In this context, various 2-oxopyridine-3-carbonitriles and their 2-amino isosteres have revealed promising molecular-based anticancer activities being able to interfere with Pim-1 protooncogene, serine/threonine kinase (PIM1) Kinase and survivin protein which played articular roles in suppressing cancerous cell survival and proliferation, in addition to induction of apoptosis.…”

Melamine‐Functionalized Chitosan: A New Bio‐Based Reusable Bifunctional Organocatalyst for the Synthesis of Cyanocinnamonitrile Intermediates and Densely Functionalized Nicotinonitrile Derivatives

“…The α,β‐unsaturated products obtained by the Knoevenagel condensation have been widely used as appropriate intermediates for the synthesis of pharmaceutically interesting heterocyclic compounds such as nicotinonitrile scaffolds . The useful strategy for the synthesis of medicinal potent functionalized 2‐amino‐6‐(2‐oxo‐2 H ‐chromen‐3‐yl)‐4‐arylnicotinonitrile derivatives is based on the catalytic Knoevenagel condensation between malononitrile/ethyl cyanoacetate and diverse aldehydes following by aryl ketones and ammonium acetate . In continuation of our interest to develop mild efficient organocatalysts for different organic reactions, herein, we report a novel heterogeneous organocatalyst and bio‐based covalently‐modified chitosan using 1,3‐dibromopropane and melamine (Cs−Pr−Me, 1 ) for the Knoevenagel condensation of aldehydes with malononitrile/ethyl cyanoacetate to form cyanocinnamonitrile intermediates.…”