基于薯蓣皂苷元催化合成N-甲基吲哚孕烯醇酮化合物及其抗肿瘤活性OA北大核心CSTPCD

The D-ring C16 position of 16-dehydropregnenolone acetate(16-DPA),a precursor of steroidal drugs,was modified using N-methylindole,and the inexpensive catalytic system of ZrCl4-ethyl acetate was employed to synthesize sixteen(3β-acetyloxy-16α-3'-indolopregnenolone compounds)as well as to synthesize six 3β-hydroxy-16α-3'-indolone pregnenolone derivatives.The method has the advantages of high yield,good stereoselectivity and substrate adaptability.Twenty-two compounds were tested for antitumor activity in triple-negative breast cancer cells(MDA-MB-231)by thiazolyl blue(MTT)assay.The preliminary test results showed that among the 3β-acetoxy-16α-3'-indolopregnenolone compounds,compounds 6h and 6i had better cancer inhibitory activities against MDA-MB-231 cancer cells with median inhibition concentration(IC50)of 18.07 and 23.22 μmol/L,respectively,whereas all of compounds 7a—7f had better cancer inhibitory activities against MDA-MB-231 cancer cells,among which compound 7e showed the best antitumor activity with an IC50 of 12.50 μmol/L.These compounds provide some references for drug screening.