title: Novel spiropyrazolone antitumor scaffold with potent activity: Design, synthesis and structure-activity relationship.
abstract: Phenotypic screening of high quality compound library is an effective strategy to discover novel bioactive molecules. Previously, we developed the divergent organocatalytic cascade approach to efficiently construct a focused library with scaffold diversity and successfully identified a novel spiropyrazolone antitumor scaffold. Herein, a series of spiropyrazolone derivatives were designed, synthesized and assayed. Most of them showed good in vitro antitumor activity with a broad spectrum. Preliminary structure-activity relationship for the substitutions and the stereo configuration were obtained. Compound 5k showed good antitumor activity and could effectively induce cancer cell apoptosis, which represents a good starting point for the development of novel antitumor agents.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Shanchao
authors.initials: S
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical Research Center, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Miao
authors.affiliation: Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address: suhuash@sina.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: zhangwnk@hotmail.com.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: shengcq@hotmail.com.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D047069:Pyrazolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047069:Pyrazolones; D013141:Spiro Compounds
keywords: Antitumor; Cancer cell apoptosis; Spiropyrazolone; Structure–activity relationship