Eco-friendly Synthesis of Indole Conjugated Chromeno[B]Pyridines as Anti-cancer agents and their Molecular Modelling Studies

Abstract: Many medicinally active new chemical entities depend on indole-conjugated chromeno[ b]pyridine derivatives as a building block. The synthesis of 4-(1H-indol-3-yl)-3,4-dihydro-1Hchromeno[ 4,3-d]pyrimidine-2,5-dione 4 was developed in the current study by treating 4-hydroxy- 2H-chromen-2-one 1, indole aldehydes 2, and urea/thiourea 3 in the presence of L-proline as catalyst in ethanol as solvent for 2-3 hours at 70-75°C with yields of 80-85%, and their structures were characterized by various spectral techniques. The synthesized compounds were tested for their potential to inhibit cancer growth in HepG2 and MDA-MD-231 cells. Out of all the compounds, compound 4b displayed noteworthy cytotoxicity with IC50 values of 8.1 and 9.2 μM against HepG2 and MDAMD- 231, respectively. Additionally, insilico studies indicated that compound 4b had favorable binding energy (-7.8 kcal/mol) when compared to the co-crystal ligand (LS5) in inhibiting the human cyclin-dependent kinase 2 (CDK2) protein.