title: Cyclic marinopyrrole derivatives as disruptors of Mcl-1 and Bcl-x(L) binding to Bim.
abstract: A series of novel cyclic marinopyrroles were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-x(L), was evaluated using ELISA assays. Both atropisomers of marinopyrrole A (1) show similar potency. A tetrabromo congener 9 is two-fold more potent than 1. Two novel cyclic marinopyrroles (3 and 4) are two- to seven-fold more potent than 1.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education and State Key Laboratory of Biotherapy, Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. chengchunwei666@163.com.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. yan.liu@unmc.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. maria.balasis@moffitt.org.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Balasis
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. nsimmons@scripps.edu.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Simmons
authors.affiliation: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. jerry.li@ucsf.edu.
authors.forename: Jerry
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education and State Key Laboratory of Biotherapy, Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. haoright@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education and State Key Laboratory of Biotherapy, Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. pande179@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Pan
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education and State Key Laboratory of Biotherapy, Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. qinyong@cqu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. kcn@rice.edu.
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.affiliation: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. said.sebti@moffitt.org.
authors.forename: Said M
authors.initials: SM
authors.lastname: Sebti
authors.affiliation: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. rongshi.li@unmc.edu.
authors.forename: Rongshi
authors.initials: R
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy; D002384:Catalysis; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000494:pharmacology*; D008565:Membrane Proteins / Q000737:chemistry*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D007202:Indicators and Reagents; C579095:MCL1 protein, human; D008387:Marine Toxins; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins; D011758:Pyrroles; D051020:bcl-X Protein