Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives
| Autor: | Qi Chen, Huaji Guan, Rihui Cao, Wenlie Peng, Anlong Xu, Xuerui Hou, Yan Ma, Hongsheng Chen |
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| Rok vydání: | 2004 |
| Předmět: |
Drug-Related Side Effects and Adverse Reactions
Stereochemistry Neurotoxins Clinical Biochemistry Substituent Pharmaceutical Science Antineoplastic Agents Binding Competitive Biochemistry Chemical synthesis Inhibitory Concentration 50 Mice Structure-Activity Relationship chemistry.chemical_compound Harmine Drug Discovery Tumor Cells Cultured medicine Animals Molecular Biology Alkyl chemistry.chemical_classification Alkaloid Organic Chemistry Tryptophan Neurotoxicity medicine.disease Acute toxicity chemistry Toxicity Molecular Medicine Carbolines |
| Zdroj: | Bioorganic & Medicinal Chemistry. 12:4613-4623 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2004.06.038 |
| Popis: | A series of novel 9-substituted β-carboline derivatives was synthesized from harmine and l -tryptophan, respectively. Cytotoxic activities of these compounds in vitro were investigated. The results showed that most compounds of 9-substituted β-carboline derivatives had more remarkable cytotoxic activities in vitro than their corresponding parent compounds. Acute toxicities and antitumor effects of the selected β-carboline derivatives in mice were also examined. The results demonstrated that a short alkyl or benzyl substituent at position-9 increased the antitumor activities significantly and a ethoxycarbonyl or carboxyl substituent at position-3 reduced the acute toxicity and neurotoxicity of these β-carboline derivatives dramatically. Moreover the compounds both with an alkoxycarbonyl or carboxyl substituent at position-3 and a short alkyl or benzyl substituent at positon-9 exhibited more significant antitumor activities and lower acute toxicities and neurotoxicities than the other compounds. The compound 8c , having an n -butyl and a carboxyl substituent at position-9 and 3, respectively, was found to have the highest antitumor effect and the lowest acute toxicity and neurotoxicity. These data suggested that ( 1 ) appropriate substituents at both position-9 and 3 of β-carboline derivatives might play a crucial role in determining their enhanced antitumor activities and decreased acute toxicities and neurotoxic effects; ( 2 ) the β-carboline derivatives have the potential to be used as antitumor drug leads. |
| Databáze: | OpenAIRE |
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