[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

A series of 2-amino-5-oxo-4-(1H-pyrazol-5-yl)-5H-chromeno[4,3-b]pyridine-3-carbonitriles was synthesized with good yields of 87-90% by reacting 4-amino-2H-chromen-2-one with 1H-pyrazole-5-carbaldehyde and malononitrile at 70-75 degrees 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-1H-pyrazol-5-yl)-5-oxo-5H-chromeno[4,3-b]pyridine-3-carbonitriles were identified as most active compounds: IC50 values of 9.2 and 8.9 mu M 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-1H-pyrazol-5-yl)-5-oxo-5H-chromeno[4,3-b]pyridine-3-carbonitrile, which is higher than positive control co-crystal ligand 2HC (-5.4 kcal/mol).

Automated summary

A series of 2-amino-5-oxo-4-(1H-pyrazol-5-yl)-5H-chromeno[4,3-b]pyridine-3-carbonitriles were synthesized using BMIM[OH] as ionic liquid, with good yields of 87-90%. The synthesized derivatives exhibited cytotoxic activity against PC-3 and HepG2 cells, with 2-amino-9-ethyl-4-(1-methyl/ethyl-1H-pyrazol-5-yl)-5-oxo-5H-chromeno[4,3-b]pyridine-3-carbonitriles identified as the most active compounds. These compounds also showed binding affinity towards human carbonic anhydrase protein.