Crystal structure, Hirshfeld surface analysis, DFT calculations and molecular docking studies on pyridine derivatives as potential inhibitors of NAMPT

Abstract

Abstract The crystal structure of 4-(4-fluorophenyl)-2-(1H-indol-3-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ia) and 2-(1H-indol-3-yl)-4-(thiophen-2-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ib) were elucidated by single crystal X ray diffraction. The central piperidine ring adopts twisted conformation, the piperidine of octahydroindolizine ring is in half chair conformation and the pyrrole ring is in twisted envelope conformation in both the compounds (Ia) and (Ib). Details of the preparation, crystal structure determination and intra- and inter- molecular interactions of the compounds are given. Intermolecular interactions were also studied by Hirshfeld surface analysis. The structures of both compounds were optimized by density functional theory (DFT) calculations using B3LYP hybrid functional with 6–311G(2d,2p)level basis set. The molecular docking study of synthesized compound with an enzyme, namely, Nicotinamidephosphoribosyltransferase (NAMPT) which increases sensitivity to apoptosis in both NAMPT-expressing cells and tumorspheres has also been carried out.