title: Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors.
abstract: A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin). Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable.
authors.affiliation: Laboratory of Computer-Aided Drug Design &amp; Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. caoshuangknight@163.com.|Hubei Key Laboratory of Novel Chemical Reactor and Green Chemical Technology, Wuhan Institute of Technology, Wuhan 430073, Hubei, China. caoshuangknight@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Cao
authors.affiliation: Laboratory of Computer-Aided Drug Design &amp; Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. 21cc@163.com.
authors.forename: Ruiyuan
authors.initials: R
authors.lastname: Cao
authors.affiliation: Hubei Key Laboratory of Novel Chemical Reactor and Green Chemical Technology, Wuhan Institute of Technology, Wuhan 430073, Hubei, China. liuxialing@hotmail.com.
authors.forename: Xialing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Hubei Key Laboratory of Novel Chemical Reactor and Green Chemical Technology, Wuhan Institute of Technology, Wuhan 430073, Hubei, China. rosen_luo@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Laboratory of Computer-Aided Drug Design &amp; Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. zhongwu@bmi.ac.cn.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhong
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C005465:benzothiazole
keywords: PI3Kβ; docking; kinase inhibitor; mTOR