Synthesis And Antitumor Activity Of Sulforaphane Analogues Containing Benzene Ring Structure

Objective:Epidemiological studies have found that increasing the intake of cruciferous vegetables can significantly reduce the incidence of cancer,of which sulforaphane plays an important role.Studies have shown that sulforaphane（SFN）is the best natural active ingredient found in vegetables so far,and has become an important anti-tumor drug candidate.However,SFN is volatile,sensitive to light,temperature,and p H,greatly limiting the clinical use of SFN.In this paper,sulforaphane was used as a lead compound to chemically synthesize sulforaphane analogues containing benzene ring.The differences in stability and antitumor activity between synthetic analogues and sulforaphane were compared to provide theory and research for the development and utilization of sulforaphane.Methods:1.In order to improve its physical and chemical properties and stability,a1,3-disubstituted benzene ring structure into the butyl carbon chain of SFN and designed to synthesis 12 SFN analogs containing an aromatic ring structure.2.Take the SFN as control,and the stability of the synthesized SFN analog was compared according to the change of the absorbance value at the maximum absorption wavelength.3.Take the SFN as control,using CCK-8 kit,evaluation of anti-tumor activity of synthetic SFN analogs,which act on the human hepatoma cell line（Hep G2）,non-small cell lung cancer cell line（A549）,human ovarian cancer cell line（OVCAR-3）,and human gastric adenocarcinoma cell line（SGC-7901）was carried out.Results:1.12 SFN analogs containing a 1,3-disubstituted benzene ring structure were chemically synthesized,and their structural characterization was confirmed by NMR and MS.2.The absorbance value of the synthesized SFN analogues did not change much with the settling time.The absorbance value of the SFN analogs became smaller with the set time,which indicated that the SFN analogs did not change and decomposed,which proved that the stability of the synthesized SFN analogs was obtained.Improved.3.Compound 2-1(A549,69.35±0.8548μmol·L^-1)and compound 3-8(Hep G2,58.38±0.8937μmol·L^-1)inhibited tumor cell proliferation activity and SFN(A549,63.18±0.5846μmol·L^-1)inhibition of tumor cell proliferation activity was comparable,and compounds 2-1,3-3,3-5,3-8 showed some selectivity for different tumor cell lines.Conclusion:The synthesized 12 SFN analogs were confirmed by NMR and MS.The stability was improved compared with SFN.Compared with SFN,the inhibition of tumor cell proliferation activity decreased slightly,but compound 2-1 3-3,3-5,3-8 showed certain selectivity to different tumor cell lines,which has the potential for further research and development,and also provided a theoretical basis for the development and design of SFN analogues.