title: Benzothiazoles exhibit broad-spectrum antitumor activity: their potency, structure-activity and structure-metabolism relationships.
abstract: An antitumor activity oriented benzothiazole sublibrary was constructed from a hit compound 3 via a five stepwise procedure. All target compounds were screened for their antitumor activity against 60 human cancer cell lines. Compounds 9p, 12d and 12i, showing higher potency than hit 3, were identified. Particularly, the compound 9p gave its average 50% growth inhibition (GI₅₀) at 0.38 μM. Furthermore, incubation in human liver microsome primarily proved their metabolic stability in vitro. General structure-activity and structure-metabolism relationships were both summarized, which provides information on further strategically optimization.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2A Nanwei Rd., Xicheng Dist., Beijing 100050, PR China.
authors.forename: Xilei
authors.initials: X
authors.lastname: Xie
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2A Nanwei Rd., Xicheng Dist., Beijing 100050, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2A Nanwei Rd., Xicheng Dist., Beijing 100050, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2A Nanwei Rd., Xicheng Dist., Beijing 100050, PR China; Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Haidian Dist., Beijing 100084, PR China; Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Haidian Dist., Beijing 100084, PR China. Electronic address: gangliu27@tsinghua.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles
keywords: Antitumor activity; Benzothiazole; Structure–activity relationships; Structure–metabolism relationship