title: Discovery of novel steroidal pyran-oxindole hybrids as cytotoxic agents.
abstract: A series of novel steroidal pyran-oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C-C and C-O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC50 values of 4.43 and 8.45 μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: zzuyubin@hotmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Qi
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: shlh@zzu.edu.cn.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Shan
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: dqyu@imm.ac.cn.
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D000078183:Oxindoles; D011714:Pyrans / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D000078183:Oxindoles; D011714:Pyrans; D013256:Steroids; C022960:2-oxindole
keywords: Apoptosis; Cell cycle arrest; Cytotoxicity; Pyran–oxindole hybrids