Study On Metallic Ion Recognition And Biological Properties Of B-norcholesteryl Benzimidazole Compounds

Compounds with heterocyclic structures usually have good antibacterial,anti-inflammatory and anti-tumor activities,and are often used in the fields of pesticides and medicine.Previous studies have found that some B-norcholesteryl benzimidazole compounds synthesized by our group have good antitumor activity in vitro.In order to expand the application of these compounds,the mechanism of their antitumor activity is studied in depth.In this paper,three parts are designed: firslyt,three steroidal benzimidazole compounds are selected to study the metal ion recognition,and the application of metal ion fluorescence sensor is explored.Secondly,the interaction between steroid benzimidazole compounds and DNA in simulated physiological environment were studied.Third,the interaction between steroidal benzimidazole compounds and protein were studied,these results provide a theoretical basis for the design of new antitumor drugs.The specific contents of the study are as follows:1.Using B-norcholesteryl benzimidazole as metal ion receptors.The changes of UV and fluorescence spectra of 12 different metal ions(Co2+、K+、Na+、Li+、Pb2+、Ca2+、Zn2+、Sr2+、Ni2+、Ag+、Hg2+、Cu2+)in anhydrous ethanol solution were studied.It is found that this kind of B-norcholesteryl benzimidazole has high selectivity and anti-interference to Cu2+.This kind of compound can form 1:1 complex with Cu2+.2.In simulated physiological environment,the interaction mechanism of three B-norcholesteryl benzimidazole compounds with ct-DNA was studied by UV,fluorescence,circular dichroism and viscosity methods.UV spectra showed that all three compounds can induce the shift of UV absorption peak position of ct-DNA and induce the decolorization effect of ct-DNA.It is inferred that the intercalation between the compound and ct-DNA.The quenching process of three compounds with ct-DNA is caused by static quenching process.The viscosity test showed that the concentration of the compound increased with the increase of the viscosity of DNA,which indicated that the compound was inserted into the base pair of DNA resulted in the increase of the double chain of DNA and the increase of its viscosity.The experimental results of circular dichroism show that the positive absorption peak intensity increases at 273 nm and decreases at 245 nm due to the insertion of the compound into the base pair of DNA,which results in the π→π* electron transition of base pair superposition.It hinders the close superposition of adjacent base pairs,which makes the DNA double helix loose and decreases the negative peak strength.3.In clinical disease studies,drugs targeting the apoptotic pathway have been shown to increase the sensitivity of tumor cells to chemotherapy and radiotherapy.Three kinds of cholesteroidal benzimidazole compounds were selected to study the anticancer effect and mechanism in He La(cervical cancer cell)and SKOV3(human ovarian cancer cell).The expression of p21、p53 mRNA and p21、p53 protein were detected by QPCR and Western Blot respectively.The results showed that these three cholesteric benzimidazole compounds were a good apoptosis-promoting factor,p21、p53,which had a certain effect on the apoptosis of cervical cancer and ovarian cancer cells induced by three B-norcholesteryl benzimidazole compounds.