Discovery of benzochromene derivatives first example with dual cytotoxic activity against the resistant cancer cell MCF-7/ADR and inhibitory effect of the P-glycoprotein expression levels.

A series of 1H-benzo[f]chromene moieties (4a-z) were synthesised under Ultrasonic irradiation and confirmed with spectral analyses. Derivative 4i solely possessed an X-ray single crystal. The anti-proliferative efficacy of the desired molecules has been explored against three cancer cells: MCF-7, HCT-116, and HepG-2 with the cytotoxically active derivatives screened against MCF-7/ADR and normal cells HFL-1 and WI-38. Furthermore, compounds 4b-d, 4k, 4n, 4q, and 4w, which possessed good potency against MCF-7/ADR, were tested as permeability glycoprotein (P-glycoprotein [P-gp]) expression inhibitors. The attained data confirmed that 4b-d, 4q, and 4w exhibited strong expression inhibition against the P-gp alongside its cytotoxic effect on MCF-7/ADR. The western blot results and Rho123 accumulation assays showed that compounds 4b-d, 4q, and 4w effectively inhibited the P-gp expression and efflux function. Meanwhile, 4b-d, 4q, and 4w induced apoptosis and accumulation of the treated MCF-7/ADR cells in the G1 phase and 4k and 4n in the S phase of the cell cycle.

Ecofriendly Long Life Nanocomposite Sensors for Determination of Carbachol in Presence of Choline: Application in Ophthalmic Solutions and Biological Fluids.

Several emerging nano scale forms of carbon are showing great promise in electrochemical sensing such as graphene and multi-walled carbon nanotubes (MWCNTs). Herein we present an ecofriendly method to fabricate long life and sensitive ion selective sensors based on graphene and MWCNTs nanocomposites with no need for volatile organic solvents. Both sensors were fabricated, for the analysis of carbachol in ophthalmic solutions, plasma and urine where ion- association complex was formed between cationic carbachol and anionic Sodium tetra phenyl borate (NaTBP) in a ratio 1:1. Both sensors were evaluated according to the IUPAC recommendation data, revealing linear response in the concentration range 10-7 M to 10-2 M with near Nernstian slopes 50.80 ± 5 and 58.14 ± 3 mV/decade and correlation coefficients 0.9992 and 0.9998 for graphene and MWCNTs based sensors, respectively. Both sensors were successfully applied as stability indicating method for the analysis of carbachol in presence of its metabolite choline, in ophthalmic preparations, in plasma and urine showing good recovery percentage values. MWCNTs based sensor showed some advantages over graphene sensor regarding lower limit of detection (LOD), longer life time and higher selectivity towards carbachol. Statistical comparison of the proposed sensors with the official method showed no significant difference for accuracy and precision.