title: Design, synthesis and structure–activity relationship studies of morpholino-1H-phenalene derivatives that antagonize Mcl-1/Bcl-2.
abstract: We report herein characteristic studies of Mcl-1 and Bcl-2 dual inhibitors. It was found that a protruding carbonyl group forming hydrogen bond with R263 plays a predominant role compared with the hydrophobic group that occupies the p2 pocket. A series of dual inhibitors representing different parts of the morpholino-1H-phenalene were designed, synthesized and evaluated.
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian, China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Li
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Liang
authors.forename: Ting
authors.initials: T
authors.lastname: Song
authors.forename: Pengchen
authors.initials: P
authors.lastname: Su
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D060172:Morpholinos / Q000737:chemistry*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043803:Phenalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D060172:Morpholinos; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D043803:Phenalenes; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Dual inhibitors; Hydrogen bond; Apoptosis; Mcl-1; Bcl-2