Steroidal esters of the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl)amino-phenyl]butanoic acid (2-PHE-BU)
| Autor: | Anna I. Koutsourea, Georgios N. Pairas, Manolis A. Fousteris, Ioanna C. Papaconstantinou, Athanasios D. Papageorgiou, Sotiris S. Nikolaropoulos |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research chemistry.chemical_element Conjugated system Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Toxicity Tests Animals Organic chemistry Computer Simulation Pharmacology (medical) Antineoplastic Agents Alkylating Biological evaluation Pharmacology Mice Inbred BALB C Leukemia P388 Chemistry Esters Nitrogen Nitrogen mustard Oncology Biochemistry Mice Inbred DBA Reduced toxicity Nitrogen Mustard Compounds Toxicity Computer-Aided Design Female Steroids |
| Zdroj: | Anti-Cancer Drugs. 24:52-65 |
| ISSN: | 0959-4973 |
| DOI: | 10.1097/cad.0b013e328357f687 |
| Popis: | On the basis of the results of in-silico predictions and in an effort to extend our structure-activity relationship studies, the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl) amino-phenyl]butanoic acid (2-PHE-BU) was synthesized and conjugated with various steroidal alcohols. The resulting steroidal esters were evaluated for their in-vivo toxicity and antileukemic activity in P388-leukemia-bearing mice. The new derivatives showed significantly reduced toxicity and marginally improved antileukemic activity compared with free 2-PHE-BU. Nevertheless, they did not prove to be superior either to the template steroidal ester used for in-silico predictions or to previously synthesized steroidal esters of aromatic nitrogen mustards. The results obtained indicate that in-silico design predictions may guide the design and synthesis of new bioactive steroidal esters, but further parameters should be considered aiming at the discovery of compounds with optimum activity. |
| Databáze: | OpenAIRE |
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