Synthesis And Activity Studies Of Fluorinated Stilbene CA-4 Analogues

Polyhydrostilbenes (PHS) are collectively referred to as a class of substances having a phenolic hydroxyl derivative of a polystyrene nucleus or a polymer thereof. Recent studies show that PHS has a wide range of biological activity. Pettit reports that cis PHS combretastatin A-1 has the function of interfering with microtubules, leading to cellular dysfunction to achieve antitumor effects. CA-4 is a natural stilbene product isolated from the combretum caffrum of South Africa affrum, which can inhibit the polymerization of tubulin and has some antitumor activity, and its structure is simple and it is difficult to produce drug resistance. Due to the instability of the cis-structure of CA-4 itself, it is necessary to modify the structure. The structural modification of CA-4 is also a hot spot for researchers to study.Therefore, based on the basic principles of drug design, the structural modification and transform of the stilbene CA-4 in order to obtain high bioactivity compounds is a valuable research.In this thesis, nineteen fluorine diphenylethene CA-4 analogues were designed by computer-aided drug design. The structures of the synthesized compounds were characterized and we studied its antitumor activity in vitro, and the binding sites of CA-4 and its analogues with micro tube protein were obversed by molecular docking, which nicely explain the interaction between CA-4 and its derivatives and tubulin. In this paper, we also studied the ability of these compounds to clear free radicals. And then we analyzed the impact of different structural changes on the activity by combining with anti-tumor activity and antioxidant activity values. We found that the activity values increased if the 4-methoxy group of A-ring was replaced by hydroxyl, while the activity values decreased with hydroxyl to replace other sites of the methoxy group. We expect to discuss whether there is interaction between the anti-tumor mechanism and the antioxidant mechanism, which may provide guidance for further modified of CA-4.