Synthesis And Antitumor Activity On The B-norcholesteryl Derivatives

Steroidal compounds are a class of natural products which exist widely in nature.In addition to their function as hormone,steroidal compounds also have different physiological activitie,such as antibacterial,antitumor,etc.Common steroids natural products in animals and plants are bile acids,sterols,sex hormones,etc.Cholesterol,as one of the natural steroids,is an important raw material for the synthesis of steroid hormones and vitamin D.In recent years,the application of steroidal drugs in the medical field has been expanding.Scientists found that the introduction of nitrogen-conting functional groups on the steroid ring,or the introduction of N atoms in the steroid nucleus,or changing the structure of steroid nuclei,will make the steroid has a unique biological activity even beyond the parent compound.In this study,some cholesterol derivatives had been synthesized by using a cholesterol as a raw material,modificating and renovating the cholesterol derivatives,and introducing atoms such as N atoms and O atoms.All the compounds were characterized by IR,NMR and HREIMS.The antiproliferative activity of the compounds against differengt carcinoma cells was assayed.In the first part: Referring to the biodegradation procedure of cholesterol in human body,6 of reductive products and oxidation products had been synthesized.Using cholesterol as a material,Compours were constructed through Ozone oxidation,cyclizative condensation,reduction and oxidation reaction.The anti-tumor activity of cholesterol catabolite in vitro was tested.On the basis of this study,3-acyloxy-B-norcholesteryl-6-carboxylic acid and 3-acyloxy-B-norcholesteryl-6-ol were obtained by introducing of different esterfunction,then oxidizing and deoxidizing aldehyde group in position-6.This section works had synthesized 28 compounds,in which 12 intermediate products and 14 target products hadn't been reported before.All structures were determined by IR,NMR and HREIMS.The antiproliferative activity of these compounds in vitro was evaluated against SKOV3(ovarian cancer),T47D(Human mammary duct cancer cell),MCF-7(human breast cancer cell)and normol kidney epithelial cells(HEK293T).In the second part: On the basis of the first part of the work,a series of3-acyloxy-B-norcholesteric-6-thiosemicarbazide(6-CH3)had been synthesized by introducing thiosemicarbazide at position-6 and retainning ester at position-3.In addition,B-norcholesteryl were prepared by using similar approach.5 of B-norcholesteryl-6-thiosemicarbazide(6-CH3)with different oxime ether functional group at position-3 had been synthesized by Jone's oxidationsition,and then introduced 4-methylthio-semicarbazone.In this paper,25 of compounds were synthesized,in which 8 intermediates and 12 target products hadn't been reported before.All compounds were characterized by IR,NMR and HRMS.In addition,The antiproliferative activity of these compounds in vitro was evaluated against SKOV3(ovarian cancer),T47D(human mammary duct cancer cell),MCF-7(human breast cancer cell)and normol kidney epithelial cells(HEK293T).In the third part: based on the work of the first part,the result shows that3-acyloxy-B-norcholesteryl-6-carboxylic acid has great Antitumor Activity in vitro.8 of B-norcholesteric derivatives with amide structure had been synthesized by introducing amide bond at position-6.All compounds were characterized by IR,NMR and HRMS.The antiproliferative activity of these compounds in vitro was evaluated against SKOV3(ovarian cancer),T47D(Human mammary duct cancer cell),MCF-7(human breast cancer cell)and normol kidney epithelial cells(HEK293T).In this paper,67 compounds had been synthesized,41 of which are end products and 26 are intermediates,41 were end products.In 67 compounds,54 compounds had not been reported before.