Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives

Abstract

A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds5a,5d,and5fwere solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds4a,4b,4c,4d,4e,4f, and4gare potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT), andN-acetylcysteine. Compounds4a–4e(IC50=101.8±0.8–124.4±4.4 μM) and4g(IC50=104.1±1.9 μM) were more potent antioxidants than the standard (BHT,IC50=128.8±2.1 μM). The enzyme inhibition potential of these compounds was also evaluated,in vitro, against thymidine phosphorylase,α-glucosidase, andβ-glucuronidase enzymes. Compounds4c,4h,4o,4p,4q, 5f,and5mwere found to be potentα-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds4v,and5hwere found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x,4z,and5a–5m) were found to be noncytotoxic against human prostate (PC-3), Henrietta Lacks cervical (HeLa) and Michigan Cancer Foundation-7 breast (MCF-7) cancer cell lines, and 3T3 normal fibroblast cell line, except4ywhich was cytotoxic against all the cell lines.