Synthesis And Bioactivity Of Paeonol And 1,8 - Naphthalene Amide Derivatives

With the development of industrial and improvement of people’s living standards,the cancer has become one of the major diseases which serious impact on human’s health and lives. Due to restrictions of the plant resources, growth environment and plant contents, the natural drug have been unable to meet the current demand for the treatment of cancer. Therefore, finding new type highly efficient anticancer drugs has become an important direction and the basic way in the treatment of cancer at 21 st century.In order to exploit novel lead structures, we immerge the bioactive unit dithiocarbamate into the paeonol and 1,8-naphthalimide framework based on the bioisosterism and the connecting principle of actively biological groups; At the same time, we immerge the paeonol and 1,8-naphthalimide units into the N-heterocyclic carbenes, which thirty-six kinds of new Paeonol and 1,8-naphthalimide derivatives were altogether obtained. The target compounds were structurally characterized by1 HNMR, 13 CNMR, MS and X-ray diffraction. Based on the results of antiproliferative activity and structure-acticity relationship, we succeed to find several lead structures with outstanding activity.1、Based on the bioisosterism and the connecting principle of actively biological groups, fifteen kinds of new dithiocarbamate-paeonol derivatives were synthesized.Anti-proliferative activity of these compounds was investigated by using MTT in vitro. The preliminary results found that the IC50 values of the5-acetyl-4-hydroxy-2-methoxy-benzyl-pyrrolidin-1-dithio-carboxylate(compound2-2a) for A549 and PC12 tumor lines reach the level of 0.55 and 1.71 μM, repectively,which are shown to be high cytotoxic and about 2 to 3 times more cytotoxic than cisplatin(CDDP). The IC50 values of the compound 2-3c aganist four kinds of tumor cells are equivalent to cisplatin(CDDP). It has a broad, general anti-tumor activity.Compared with paeonol, it has been remarkably improved. These studies indicated the paeonol derivatives with substituted dithiocarbamate groups on 5-position were akind of excellent antitumor precursor, which exhibited potentail in the application of biomedicine.2、Based on the bioisosterism and the connecting principle of actively biological groups, fifteen kinds of novel dithiocarbamate-1,8-naphthalimide derivatives were obtained. The anti-tumor activity and antibacterial activity of these compounds were investigated. Preliminary results found that some compounds exhibit good cytotoxicity. However, the antibacterial activity of 1,2,3-triazole-1,8-naphthalimide compounds showed very good results. The antibacterial activity of compounds 3-7a ~3-7d aganist Bacillus subtilis could reach the level of the market drug cefuroxime. It indicated very good antibacterial effect, which showed potentail in the application of biomedicine.3、Based on the connecting principle of actively biological groups, six different novel N-heterocyclic carbene gold chloride compounds. Anti-proliferative activity of these compounds was investigated by using MTT in vitro. Wherein, the anti-tumor activity of paeonol derivatives bearing 1,8-naphthalimide could not be increased, but the paeonol N-heterocyclic carbene gold chloride compound showed certain anti-tumor activity.4 、We also discussed the reduction of the 4-azido-1,8-naphthalimide with different phosphine ligands. We further found that the 4-azido-1,8-naphthalimide could be returned into 4-amino-1,8-naphthalimide using trimethylphosphine with more than 93% yield over 3 hours. Compared to the methods including the use of Pt-H and Na HS, advantage using trimethylphosphine was not only metals free but also no harmful gases. It is an efficient novel reduction method.