title: Synthesis and Biological Evaluation of Matijin-Su Derivatives as Potential Antihepatitis B Virus and Anticancer Agents.
abstract: A series of Matijin-Su (MTS, (2S)-2-{[(2S)-2-benzamido-3-phenylpropanoyl]amino}-3-phenylpropyl acetate) derivatives were synthesized and evaluated for their anti-HBV and cytotoxic activities in vitro. Six compounds (4g, 4j, 5c, 5g, 5h and 5i) showed significant inhibition against HBV DNA replication with the IC50values in range of 2.18 - 8.55 μm, which were much lower than that of positive control lamivudine (IC5082.42 μm). In particular, compounds 5h (IC502.18 μm; SI 151.59) and 5j (IC505.65 μm; SI 51.16) displayed relatively low cytotoxicities, resulting in high SI values. Notably, besides the anti-HBV DNA replication activity, compound 4j also exhibited more potent in vitro cytotoxic activity than 5-fluorouracil in two hepatocellular carcinoma cell (HCC) lines (QGY-7701 and SMMC-7721), indicating that 4j may be a promising lead for the exploration of drugs with dual therapeutic effects on HBV infection and HBV-induced HCC.
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, P. R. China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Qiu
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002, P. R. China.
authors.forename: Bixue
authors.initials: B
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, P. R. China.
authors.forename: Qineng
authors.initials: Q
authors.lastname: Gong
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002, P. R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Pan
authors.affiliation: Tianjin Institute of Pharmaceutical Research, 308 Anshan Xi Dao, Nankai District, Tianjin, 300193, P. R. China.
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: 302 Hospital of PLA, 100 Xisihuan Zhong Road, Fengtai Beijing, 100039, P. R. China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, P. R. China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Gu
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002, P. R. China.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004151:Dipeptides; C000595690:N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol
keywords: Antihepatitis B virus activity; Cytotoxic activities; MTS Derivatives; Structure-Activity Relationships; Synthesis