Design,Synthesis And Anti-tumor Activity Of Novel 4-thienyl Substituted Pyrroles

With the development of economy,human lifestyle and diet structure have changed a lot.Influenced by many factors,tumor now has become one of the common and frequently occurring diseases that threaten human's life and health.There is an upward trend in malignant tumor of the morbidity and mortality,and it is one of the world's largerst public health problems,severely threathening human health.Since the second half of the 20th century,the number of people with malignant tumors growed in a rate of 3%⁵%.With the improvement of people's living standard and the progress of the medical conditions,some diseases,which were considered incureable in the past,have effective treatment now;however,the treatment of malignant tumor is still a tough problem,and people died because of cancer have an increased trend.Now the main treatments for cancer are surgery,chemotherapy and radiation therapy,etc.Surgery and chemothrerapy are essential in clinical,but most anti-tumor drugs have side effect on normal cells while killing cancer cells,besides tumor cells may have tolerance to the drug,which causes great reduce in clinical effect.Cancer causes lot of pain to patients and brings heavy burdens to families and society as well,so drug developers still need to put great afford in developing anti-tumor drugs with higher selectivity,better curative effect and less side effect.Our team has been studying the anti-tumor effect of pyrrole compounds for a long time;in previous reports the substituent groups on position 4 of pyrrole nucleus mainly were substituted phenyls.In this study,we design to replace the phenyls with thienyls on position 4.Since thiophenes have special activity as heterocyclic compounds and play an important role in new drug development,we decide to graft thienyls on position 4 of pyrrole nucleus to estimate the anti-tumor activity of those4-thienyl substituted pyrrole compounds.After analyzing the structure-activity relationships of more than 400pyrrole compounds synthesized by our team,we designed and synthesized six series of 4-thienyl substituted pyrrole compounds,totally53;and all target compounds weren't reported before.All the targrt compounds were characterized by ¹H NMR,¹³C NMR and HRMS.Anti-tumor activity was estimated by MTT assay in vitro;1 normal cell and 9 kinds of tumor cell strains were choosen as subject cells.The results suggested that some target compounds showed strong(IC₅₀?20?mol/L)or moderate(20?mol/L<IC₅₀?50?mol/L)cell proliferation inhition activity,meanwhile didn't have obvious effect on normal cell,which were with high-selectivity.HCT-116,Hela and SGC-7901 were sensitive to the target compounds.The IC₅₀ value of LC20 was 4.3?mol/L agasint Hela;the IC₅₀ value of LC40 was 10.5?mol/L agasint SGC-7901;the IC₅₀ value of LC49 was 10.5?mol/L agasint SGC-7901 and the IC₅₀value of LC50 was 11.1?mol/L agasint SGC-7901,which deserved further study.We summarized the structure-activity relationships of these novel 4-thienyl substituted pyrrole compounds,in order to guide the further structure modification of these compounds.