[BMIM][OH]-Mediated One-Pot Synthesis of 2-Amino-5-oxo-4-(1H-pyrazol-5-yl)-5H-chromeno[4,3-b]pyridine-3-carbonitriles as Potential Anticancer Agents

• Published in: Russian journal of general chemistry 2023, Vol.93 (1), p.227-233
• Main Authors: Srinivas, A., Shree, A. Jaya, Goud, S. Sharath Kumar
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antimitotic agents; Antineoplastic agents; Cancer; Carbonic anhydrase; Care and treatment; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Evaluation; Force and energy; Ionic liquids; Malononitrile; Pyrazole; Pyridine; Pyridines; Synthesis
• ISSN: 1070-3632; 1608-3350
• DOI: 10.1134/S1070363223010279

A series of 2-amino-5-oxo-4-(1 H -pyrazol-5-yl)-5 H -chromeno[4,3- b ]pyridine-3-carbonitriles was synthesized with good yields of 87–90% by reacting 4-amino-2 H -chromen-2-one with 1 H -pyrazole-5-carbaldehyde and malononitrile at 70–75°C for 120–150 min using BMIM[OH] as ionic liquid. Cytotoxic activity of the synthesized derivatives against PC-3 and HepG2 cells was evaluated. Among synthesized, 2-amino-9-ethyl-4-(1-methyl/ethyl-1 H -pyrazol-5-yl)-5-oxo-5 H -chromeno[4,3- b ]pyridine-3-carbonitriles were identified as most active compounds: IC 50 values of 9.2 and 8.9 µM against PC-3 and HepG2 cells, respectively. In addition, we evaluated the binding affinity of these compounds towards human carbonic anhydrase protein (PDB ID: 5BNL). The binding energy was found to be –7.1 kcal/mol for 2-amino-9-ethyl-4-(1-methyl-1 H -pyrazol-5-yl)-5-oxo-5 H -chromeno[4,3- b ]pyridine-3-carbonitrile, which is higher than positive control co-crystal ligand 2HC (–5.4 kcal/mol).