Synthesis and antitumor activity of duocarmycin derivatives: modification at the C-7 position of segment-A of A-ring pyrrole compounds
| Autor: | Masami Okabe, Akihiko Okamoto, Hiromitsu Saito, Nobuyoshi Amishiro |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Magnetic Resonance Spectroscopy
Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Spectrometry Mass Fast Atom Bombardment Biochemistry Chemical synthesis chemistry.chemical_compound Mice In vivo Drug Discovery Potency Animals Humans Pyrroles Phenols Cytotoxicity Molecular Biology Duocarmycin Pyrrole Organic Chemistry In vitro Pyrrolidinones chemistry Molecular Medicine HeLa Cells |
| Zdroj: | Bioorganicmedicinal chemistry. 8(5) |
| ISSN: | 0968-0896 |
| Popis: | A series of the C7-substituted A-ring pyrrole derivatives of duocarmycin were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. All of the C7-substituted A-ring pyrrole compounds decreased potency in vitro and in vivo. However, some showed strong antitumor activity with T/C values less than 0.3. Among them, the 7-formyl compound 5d Scheme 1. (a) NBS or NCS, CCl4, rt; (b) Ac2O, BF3·Et2O, rt; (c) Cl2CHOMe, TiCl4, CH2Cl2, rt; (d) MeOCH2COCl, AlCl3, CH2Cl2, rt; (e) NaNO2, AcOH, dioxane, −20 °C; (f) 1) NaH, 2) p-nitrophenyl 4-methoxycinnamate, DMF, −20 °C; (g) 1) HCl, 2) 4-methoxycinnamic acid, EDCI, rt; (h) DBU, CH3CN, rt. Figure options Download full-size image Download high-quality image (140 K) Download as PowerPoint slide showed remarkable potent in vivo antitumor activity and low peripheral blood toxicity, which were equal to 2c Figure 1. Structure of duocarmycins and duocarmycin derivatives. Figure options Download full-size image Download high-quality image (106 K) Download as PowerPoint slide . |
| Databáze: | OpenAIRE |
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