Design, Synthesis And Antitumor Activity Evaluation Of Novel Sulfonamide Nitrogen Derivatives

According to the reports,sulfonamides have a wide range of biological activities such as antibacterial,antivirus,antiinflammatory,antitumor and antidiabetic activities.The sulfonamides are relatively simple in chemical structures and organic synthesis.In recent years,for developing new antitumor drugs,medicinal researchers have used chemical methods to introduce other active fragments in the sulfanilamide skeleton,which can enrich the types of sulfonamides,increase the structural novelty,diversity and complexity of the sulfonamides to obtain compounds with good anti-tumor activity.Therefore,in this dissertation,the biologically active fragments of1,2,3-triazole,aminodithiocarbamate and pyridine are respectively combined with sulfonamides into the same molecule by the principle of molecular assembly.Finally,we designed a series of sulfonamide nitrogen derivatives whose structural characterization were confirmed and evaluated their antitumor activity in vitro.The specific research contents are as follows:1.According to the molecular scaffold,we designed and synthesized three series of 68 sulfonamide derivatives by using the knowledge of organic chemistry,which included 21 sulfa-triazole derivatives of series?and 25 sulfa-aminodithioformate derivatives of series?and 22 sulfa-thiomethyl pyridine derivatives of series?.All compounds were characterized by ¹H NMR,¹³C NMR,and HR-MS,and besides compound 11a,all the compounds were new ones that were unreported.2.The MTT method was used to evaluate the antiproliferatine activity of the synthesized compounds against human gastric cancer cells MGC-803,human prostate cancer cells PC-3,human liver cancer cells HepG2 or human breast cancer cells MCF-7.According to the experimental data,the structure-activity relationships were summarized,which provides the direction for further structural modification and antitumor mechanism research.The results showed:the compound 23r had the best inhibitory activity against MGC-803 cancer cells with an IC₅₀0 value of 3.33?M;the compound 11l had the best inhibitory activity against PC-3 and MCF-7cancer cells with IC₅₀0 values of 4.08?M and 15.7?M,respectively;the compound 23o had the best inhibitory activity against HepG2 cancer cells with an IC50 value of 1.20?M.Compounds 11l?23o?23p?23r?23v had broad-spectrum anti-tumor activity and were superior to the positive control drug 5-Fu in the activity of the tested three tumor cells.