Synthesis, Crystal Structure, Hirshfeld Surface Analyses and Biological Activity of Novel Cinnamide Derivatives as Neuroprotective Drugs

Abstract

The p-methoxycinnamoyl group contained in the compounds extracted from Scrophularia buergeriana, which is a traditional medicinal herb in China, exhibits a remarkable neuroprotective effect. Based on the p-methoxycinnamoyl group, these two cinnamide derivatives, namely, (E)-3-(4-bromophenyl)-1-(4-(4-chlorobenzyl)piperazin-1-yl)prop-2-en-1-one (6a) and (E)-1-(4-(4-chlorobenzyl)piperazin-1-yl)-3-(4-chlorophenyl)prop-2-en-1-one (6b), were designed and synthesized. The target compounds were represented by High-resolution mass spectra, ¹H NMR spectra, ¹³C NMR spectra, and single-crystal X-ray diffraction. According to the results of single-crystal X-ray diffraction, indicating that compound 6a crystallizes in the monoclinic system and compound 6b crystallizes in the triclinic system, and they both have a stacked-layer 3-D structure. Hirshfeld surface indicated that compounds 6a and 6b exist H…H, O…H, C…H, and π…π intermolecular interactions. Furthermore, their neuroprotective effects were further evaluated against glutamate-induced PC12 cell injury. These results indicate that the target compounds exhibit potent activities against glutamine-induced neurotoxicity in PC12 cells. In vivo experiments demonstrated that compounds 6a and 6b have good protective effects in high doses on bilateral common carotid artery ligation.