Design, Synthesis And Biological Activity Evaluation Of 2,3-Diaryl-Acrylonitrile And 3,5-Diaryl-2-Pyrazoline And Their Derivatives

Cancer has become the killer of human health in today’s society and the current number of cancer deaths each year than several million, behind to cardiovascular disease, threated seriously to human safety and health. Although there are a large number of anti-cancer drugs for clinical use, but the drug side effects and drug resistance is severely restricted the development of drugs. The new drug development faced many serious challenges, and discover the lead compounds which exhibited high efficacy and lower toxicity had became the hot spot wildly. The natural products played an important role in the history of the new drugs researching. Obtain the new drugs by modifications and structure transformation with the natural products as the lead compounds is an important way to the development of new drugs.In this paper, we found that the resveratrol (E-3,4’,5-trihydroxy stilbene) has a series of biological activities such as anti-tumor, anti-bacterial and anti-oxidation by literature review. However, the oxidation properties of the three phenolic hydroxyl groups, low in vivo bioavailability, and the poor efficacy limited its further development. According to the common drug design methods, which contains combination principle and bioisosterism, we designed and synthesized a series of resveratrol derivatives. We synthesized 12 of Z-2,3-diaryl acrylonitrile derivatives by introducing a cyano group to the ethylene bond on the stilbene structure, methylation of the hydroxyl groups, and Knoevevagel condensation reaction, respectively.We found that the chalcone compounds exhibited widely biological activities such as anti-tumor and anti-bacterial activity, etc., but the. toxic side effects and the low bioavailability limited its further development. We designed and synthesized two series novel compounds. N-substituted-3,5-diaryl-2-pyrazoline derivatives were obtained through Claisen-Smidtt condensation reaction, etc.All of the synthesized compounds were characterized by 1H-NMR,13C-NMR, MSand IR spectra, etc., and the biological activities of the compounds were evaluated such as anti-tumor activity and anti-bacterial activity.The results of the biological activities evaluation showed that the synthesized compounds exhibited different levels of anti-tumor activity against the human colon cancer cells HCT116, human liver cancer cells BEL7402 and the human cervical cancer cells HeLa. Among the N-chloroacetyl-3,5-diaryl-2-pyrazoline derivatives, compound 8a,8c, and 8b exhibited the best anti-tumor activity against HCT116, BEL-7402, and HeLa cancer cell line, respectively. Against HCT116 cells, the IC50 value of compound 8a was 1.13 μmol·L-1, against BEL7402 cells,8c was 4.83 jimol·L-1, and 8b was 13.21 μmol·L-1 against HeLa cells, respectively. The results of anti-bacterial activity evaluation showed that all of the synthesized compounds showed almost no anti-bacterial activity, the MIC values over than 32 μg/mL.