title: Synthesis, structure-activity relationship and biological evaluation of novel nitrogen mustard sophoridinic acid derivatives as potential anticancer agents.
abstract: A series of novel nitrogen mustard sophoridinic acid derivatives were designed, synthesized and evaluated for their cytotoxicity. Of the newly synthesized compounds, compound 6 exhibited a potent effect against hepatocellular carcinoma in vitro and in vivo. SAR analysis indicated that introduction of a nitrogen mustard group to the structure of sophoridinic acid significantly enhance the antitumor activity. Moreover, molecular docking study exhibited benzyl group introduced to the nitrogen atom at the 12-position and aryl nitrogen mustard group at the 4'-carboxyl region for compound 6 were beneficial for the higher anticancer activity. This work provides useful information for further structural modifications of these compounds and for the synthesis of new, potent antitumor agents.
authors: Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China. Electronic address: lidongdong2010@163.com.
authors: Dong-Dong
authors: DD
authors: Li
authors: Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China.
authors: Lin-Lin
authors: LL
authors: Dai
authors: Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China.
authors: Na
authors: N
authors: Zhang
authors: Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China. Electronic address: taozunweitj@163.com.
authors: Zun-Wei
authors: ZW
authors: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C000607753:sophoridinic acid
keywords: Antitumor activity; Molecular docking; Nitrogen mustard sophoridinic acid derivatives; Structure–activity relationship