Synthesis And Biological Activity Of Pyridine-containing Benzimidazoles And Their Copper Complexes

Malignant tumor,a common and frequently-occurred disease,is a serious threat to human health and is second only to the disease of heart head blood-vessel in death toll of all disease.In the ca.8 millions nascent cancer patients in one year,about 6 millions will dead,equal to each death in 6 seconds.Experts predict cancer will become the first killer of human.For a long time,the treatment of tumor is worldwide problem and is a huge challenge in medical technique.The current main treatment for cancer treatment is medicine treatment.Over the past 30 years,multiple metal complexes as diagnostics or as chemotherapy drug are applied.Copper,an important trace metal element,is second only to iron and zinc in human body.All animals and plants need copper to survive and to maintain normal physiological function.Copper plays an important role in multiple kinds of biological processes,including energy consumption,metabolism and DNA synthesis,and in biochemical functions of many kinds of enzyme,especially for cytochrome oxidase,superoxide dismutase,ascorbic acid oxidase and tyrosinase.The main functions of copper complexes are oxidation and reduction,i.e.copper can react with oxygen molecules directly with radicals engendered.It is reported that some of copper chelate has certain efficacy in the treatment of certain cancers,that a mixture of copper complexes and copper salt can effectively inhibit the proliferation of cancer cells and can induce cancer cells apoptosis.In addition,studies also show that the copper complexes of anti-cancer medicinal properties are superior to cisplatin anticancer drugs in a distinct mechanism.The copper complexes show different response,toxicity mechanism and biological distribution with the current clinical applied platinum drugs,better,especially for the traditional platinum drug resisted cancer cells.Although reports based on the molecular mechanism of its action was rarely seem,copper complexes had drawn attention for its mechanism non-identical to cisplatin.According to literatures,benzimidazole derivatives containing pyridinyl moiety have extensive biological activities,such as antibacterial,antitumor and anti-mycobacterium tuberculosis.In this report,16 compounds in this series are designed and synthesized as ligands for Copper(II)complexes.Two crystals are obtained by crystal cultivation,in which,one is benzimidazole derivative containing pyridinyl moiety,another is the corresponding copper complexes.Based on XRD,the structures of the target copper complex is detected,which is binucear bridged chelating.Structures of the other copper complexes are characterized by HRMS,which are binuceared.The antiproliferative efficacies of 29 target compounds against human liver cancer cell line HepG2 and human colorectal cancer cell line SW480 are determined by MTT method.The screening results show that the activities of copper complexes are generally better than the corresponding ligand compounds,and that some target compounds are worthy further study.