title: Efficient construction of novel D-ring modified steroidal dienamides and their cytotoxic activities.
abstract: Two series of steroidal dienamides 4a-q and 5a-f were designed, synthesized and evaluated for cytotoxic activities against five human cancer cell lines (MGC-803, EC109, PC-3, SMMC-7721 and MCF-7). The protocol developed efficiently achieved the construction of carbon-carbon double bond and selective conversion of nitrile group into carboxamide in one-pot procedure. Besides, compounds 4a-q and 5a-f showed moderate to excellent cytotoxic activities with the IC₅₀ values ranging from 0.1 to 40 μM and most of them were more potent than 5-fluorouracil. Particularly, four compounds 4d, 4e, 4q and 5a showed excellent selectivity against MGC-803 with the IC₅₀ values less than 1 μM. Flow cytometry analysis demonstrated that compound 4c caused the cellular early apoptosis and cell cycle arrest in G2/M phase in a concentration-independent manner.
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Shi
authors.forename: Jing-li
authors.initials: JL
authors.lastname: Ren
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Sun
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Qi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Ye
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Wang
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Wang
authors.forename: En
authors.initials: E
authors.lastname: Zhang
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Yu
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D013256:Steroids / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013256:Steroids
keywords: Apoptosis; Cell cycle arrest; Cytotoxicity; Dehydroepiandrosterone; Dienamides