| Cancer is a serious problem for human society,and no safe,low-toxic and effective drug has been developed to thoroughly cure this disease up to present.Therefore,the development of new-type anticancer drugs with or nontoxic effects requires a joint effort of researchers all over the world.Steroids are a common class of natural compounds which have significant physiological activities and play a vital role in the metabolism of plants,animals and microorganisms.Human beings have been devoted to the in-depth research of steroids for a very long time,and the various new functions of these compounds have gradually refreshed our cognition.For many years,the structural transformation and anti-tumor research on steroids have been a hotspot and attracted a lot of attention.At present,some of steroidal anticancer drugs(estramustine phosphate,ranimostatin,estradiol phosphate mustard,pine fennel)have been applied in clinical practice,but disadvantages such as nausea,vomiting,diarrhea,Hair loss are exist.Therefore,it is an urgent task for researchers to develop new-type,highly effective,low toxicity,targeted,anticancer drugs.It has been found form literature and our previous research work that some natural terpenes,flavonoids,steroids and alkaloids as well as their analogues containing α,β-unsaturated amine,amide,ester,alcohol,or ketone substructure usually possess good antitumor activities.Additionally,targeted therapy and new mechanism are hot spots in the current research on anticancer drugs.In recent years,some targeted drugs containing α,β-unsaturated amine,amide or ketone substructure(afatinib,dacomitinib,sunitinib)have been used in clinical treatment of cancer.With consideration of advantage of good druggablity of steroids and disadvantages of poor metabolic stability or drug resistance found in the compounds containing α,βunsaturated amine,amide,lactone,alcohol or ketone substructure,α,β-unsaturated amine,amide,alcohol or ketone substructure was embedded to the skeleton of steroids and a series of steroidal derivatives that may have both good antitumor activity and druggablity were designed.Then,dehydroepiandrosterone and estradiol as starting materials,Wittig reaction,HWE reaction,Allylic oxidation,Oppenauer oxidation and Heck reaction as key steps,49 compounds were synthesized.In addition,6 Curcurbitacin Ⅱa derivatives were prepared.39 of the total of 55 synthesized compounds were proved as the new compounds with determination and analysis of NMR,MS spectrum and X-ray crystallography,the prmary in vitro antitumor activities of these new compounds was also studied and some of these target compounds showed good antitumor activity. |
