title: Novel N-(3-carboxyl-9-benzyl-beta-carboline-1-yl)ethylamino acids: synthesis, anti-tumor evaluation, intercalating determination, 3D QSAR analysis and docking investigation.
abstract: Sixteen novel N-(3-carboxyl-9-benzyl-beta-carboline-1-yl)ethylamino acids (6a-p) were synthesized as intercalating lead compounds. In the in vitro cytotoxic assay their IC(50) values against five human carcinoma cell lines ranged from 10.95 microM to about 400 microM. On S180 mouse model eight of them exhibited anti-tumor action, four of them showed the same anti-tumor potency as that of cytarabine. The preliminary toxicity evaluation revealed that the LD(50) values of 6a-p should be more than 500 mg/kg. With CT DNA as model system an intercalating mechanism was explored. Using 3D QSAR analysis the relationship of the in vivo anti-tumor activity and the structure was quantitatively described. By docking 6a-p onto d(CGATCG)(2) oligonucleotides the intercalation was demonstrated.
authors.affiliation: College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Keduo
authors.initials: K
authors.lastname: Qian
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Susan
authors.initials: S
authors.lastname: Morris-Natschke
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005021:Ethylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D012510:Sarcoma 180 / Q000188:drug therapy; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D023382:Toxicity Tests, Acute
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D005021:Ethylamines; D007364:Intercalating Agents; D009841:Oligonucleotides; D004247:DNA