Design, Synthesis And Biological Evaluation Of Stilbene Derivatives

Stilbene derivatives, as phytoalexin, are widely distributed in plants and have become of particular interest to chemists and biologists because of their various biological activities. They are produced in plant immune system, when plants are infected by bacteria and virus or stressed by irradiation. Are there any similar effects of stilbene derivatives on animals as they do on plants? In the present work, the chemical modification of resveratrol is investigated in detail. Furthermore, virtual screening, bioactivity evaluation and structure-activity relationship (SAR) analysis are done on the designed molecules.The molecular design was carried out according to the structural characteristic of stilbenes. On the one hand, one benzen ring of stilbene was substituted by one pyridine ring for the purpose of evaluating the bioactivities of azastilbenes. On the other hand, some stilbene derivatives with different substituents in different sites were designed for the study of SAR.Synthesis of 55 stilbene derivatives, including 30 new compounds, was accomplished by means of the Wittig-Horner reaction and McMurry reaction. Complete inhibition of SARS-coronavirus was observed for two compounds at the concertration of 0.5mg/mL, and no cytotoxicity observed even at the concertration of 2.0 mg/mL.Based on FlexX, 29 candidates were selected out by docking one hundred molecules with nonnucleoside binding site of HIV reverse transcriptase. According to the consensus score and the bound conformation analysis, six compounds were chosen for anti-HIV evaluation, and all of them showed inhibitive activity on HIV. Among which, four compounds were examined repeatedly and the inhibition was higher than 60% at the concentration of 20.8μmol/L, 18.5μmol/L, 18.5μmol/L, 3.9μmol/L, respectively.In order to investigate the antioxidant activity, thirteen stilbene derivatives was examined by DPPH method. The radical scavenging ability is greatly increased by 2, 5-dihydroxy groups in the skeleton. There is a linear relationship between the maximum UV absorption wavelength and the radical scavenging ability of the compounds.A molecular database containing 166 stilbene derivatives was established. Potential antiviral targets were screened on Target Fishing Dock. Above all, 104 compounds showed inhibitive activity on HIV protease. Among them, 21 compounds were also present in 29 candidate inhibitors of HIV reverse transcriptase. It indicated that the protease and reverse transcriptase may be dual drug targets in HIV. Further, 46 molecules binding withthymidylate synthestase also imply that thymidylate synthetase may be a target. In addition, some stilbene derivatives may be effective to influenza virus. Therefore, these virtual screening results provide some useful information for the further research.