Molecular structure and spectroscopic investigations combined with hypoglycemic/anticancer and docking studies of a new barbituric acid derivative

The one-pot synthesis reaction of barbituric acid derivative, 1,3-cyclohexandione, and 4-fluorobenzaldehyde in water mediated by NHEt2 as base afforded 4 with excellent yield. The synthesized compound was characterized by spectrophotometric tools as well as X-ray single crystal diffraction technique. The stability of the nine possible isomers of the synthesized compound was studied using the B3LYP method and 6-31G(d,p) basis set. The electronic and spectroscopic properties of the most stable isomer were predicted. The UV Vis absorption spectrum displayed two bands at 203 and 257 nm in the solvent chloroform. The latter was calculated at 235.6 nm (f = 0.1995) in the gas phase due to H-2 -> L, (42%) and H-1 -> L+2 (14%) excitations. In solution, using chloroform as a solvent, a slight bathochromic shift to 237.6 nm with an increase in the absorption intensity (f = 0.2898) was predicted. The molecular orbital energy level diagram of this transition band was characterized mainly by pi-pi(star) transitions. The C-13 and H-1 NMR chemical shifts correlated well with the experimental data. The correlations had higher correlation coefficients (R-2) when solvent effects were considered. The atomic charges were calculated using natural population analysis and the charged regions were presented using a molecular electrostatic potential (MEP) map. The synthesized compound was examined as a hypoglycemic agent via inhibition of a-glucosidase and beta-glucuronidase enzymes. Its inhibitory activity against a-glucosidase was 10 times greater than the inhibitory activity of the standard drug acarbose (IC50 77.9 +/- 0.3 mu M and 840 +/- 1.73 mu M,, respectively). Moreover, the target compound was evaluated for anticancer activity against MCF-7, H460, 3T3, and Hela cell lines. It demonstrated inhibitory activity against the MCF-7 and H460 cell lines with IC50 5.80 +/- 0.12 and 19.6 +/- 0.5 mu M, respectively, in comparison to doxorubicin. The docking study was performed using the OpenEye program. (C) 2016 Elsevier B.V. All rights reserved.