This study investigated inclusion formation and the physicochemical properties of naringin/cyclodextrin through a combined computational and experimental approach. Molecular dynamics simulations were applied to investigate the thermodynamics and geometry of naringin/cyclodextrin cavity docking. The complexes were investigated by UV, FT-IR, DSC, XRD, SEM, 2D-NOSEY and 1H-NMR analyses. Clearly visible protons belonging to naringin and chemical shift displacements of the H3 and H5 protons in cyclodextrin were anticipated in the formation of an inclusion complex. Naringin solubility increased linearly with increasing cyclodextrin concentration (displaying an AL profile). The simulations indicated that the phenyl group of naringin was located deep within the cyclodextrin cavity, while the glycoside group of naringin was on the plane of the wider rim of cyclodextrin. The simulation and molecular modeling results indicate that (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) provided the more stable inclusion complex. This result was also in good concordance with the stability constants that had been determined by the phase solubility method. The consistency of the computational and experimental results indicates their reliability.

A novel C–N cleavage strategy for the regioselective synthesis of 2-nitroso heterocyclic ketene aminals (HKAs) has been established. In this procedure, the C–N bond of nitrobenzenyl nitroethene is cleaved by the oxidation reaction and selective nitroso reaction of the α-carbon in HKAs. The presented synthetic route features excellent selectivity, straightforward purification and simple starting materials.

A concise and efficient one-pot three-component synthesis of structurally diverse fluorine substituted bicyclic pyridines was constructed by simply refluxing a mixture of different types of heterocyclic ketene aminals, triethoxymethane, and fluorine-containing methylene compounds under solvent-free and catalyst-free conditions. These bicyclic pyridines are promising candidates for drug discovery; consequently, a library of fluorine substituted bicyclic pyridines was rapidly constructed in 79%–93% yields.

A method for regioselective synthesis of 9,10-dihydro-6H-chromeno[4,3-d]imidazo[1,2-a]pyridin-6-one derivatives has been developed. The reaction was readily performed by reacting inexpensive materials, 4-chloro-3-formylcoumarin and HKAs, in EtOH catalyzed by Et3N. This protocol has many advantages including convenient operation, short reaction times, green solvent, and simple purification by washing the crude products with 95% EtOH, defined as GAP (Group-Assistant-Purification) chemistry. The library of 9,10-dihydro-6H-chromeno[4,3-d]imidazo[1,2-a]pyridin-6-one derivatives has been constructed with excellent yields.

A series of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives, have been designed and synthesized in nine steps starting from ursodeoxycholic acid. The in vitro antitumor activity of the target compounds has been evaluated against HCT-116, MCF-7, K562, and SGC-7901 cell lines. The pharmacological results showed that most of the prepared compounds display excellent selective cytotoxicity toward HCT-116, MCF-7, and K562 cell lines. Particularly, compounds 10c, 10f and 10g show high inhibitory activity on these human cancer cell lines (IC50: 2.39–9.34 μM). Conversely, all compounds are generally inactive against SGC-7901, with only 10b having IC50 below 50 μM.Graphical abstractA series of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives, were synthesized and evaluated in vitro antitumor activity against HCT-116, MCF-7, K562, and SGC-7901 cell lines.Download full-size imageHighlights► Ursodeoxycholic acid derivatives, N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, were designed and synthesized. ► The in vitro antitumor activity was evaluated against four cancer cell lines. ► Three active compounds show high inhibitory activity on three human cancer cell lines.