Synthesis of resveratrol derivatives and their anti-virulence activity as T3SS inhibitors of Salmonella

Abstract

Resveratrol (RES) is a natural polyphenol that belongs to the stilbene family. Its dimer and tetramers have been reported as inhibitors of pathogenic type III secretion system (T3SS). In this study, we have synthesized 21 RES derivatives by adding different chemical entities at C-2’ position, and measured their virulence blocking properties in Salmonella by SDS-PAGE and western blot. Among them, SS-A6 with a 4-1H-pyrazole substitute at C-2’ was found to have good inhibitory activity against SipC secretion with IC50 of 34.79 μM. It also reduced the invasion of S. Typhimurium into Caco-2 cells without toxicity. Further study suggested that SS-A6 did not inhibit the expression level of SipC and the transcription of the main Salmonella pathogenicity island 1 (SPI-I) genes. The thermal shift assay suggested that SS-A6 might bind to SipC and repress the effectors secretion by affecting the formation of needle tip protein complex, and even provide a new mechanism of action.