The synthesis and evaluation of the antiproliferative activity of deacidified GEX1A analogues
| العنوان: | The synthesis and evaluation of the antiproliferative activity of deacidified GEX1A analogues |
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| المؤلفون: | Yasuo Watanabe, Shiro Soga, Hiroshi Nakagawa, Hideyuki Onodera, Imaizumi Takamichi, Kyoichiro Iida, Ran Hori |
| المصدر: | The Journal of Antibiotics. 70:675-679 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Carbamate, Stereochemistry, Carboxylic acid, medicine.medical_treatment, Antineoplastic Agents, 010402 general chemistry, 01 natural sciences, Structure-Activity Relationship, chemistry.chemical_compound, Cell Line, Tumor, Amide, Drug Discovery, medicine, Humans, Urea, Moiety, Cell Proliferation, Pyrans, Pharmacology, chemistry.chemical_classification, Natural product, 010405 organic chemistry, Amides, 0104 chemical sciences, chemistry, Drug Design, Carbamates, Fatty Alcohols, Herboxidiene, Curtius rearrangement |
| الوصف: | GEX1A/herboxidiene (1) is a natural product isolated from Streptomyces sp. and has been reported to target the pre-mRNA splicing process. Although 1 was shown to have antitumor activity in vivo, weight loss was observed in mice when 1 was consecutively administered. We assumed that the carboxylic acid moiety was one of the causes of this toxicity. In this study, a series of amide, carbamate and urea analogues of 1 were synthesized and their antiproliferative activity was evaluated in vitro. The synthesis of urea analogues featured Curtius rearrangement following amine treatment with the one-pot procedure from 1. Furthermore, a structure-activity relationship study of the urea analogues revealed that the pharmacologically preferable basic side chains were acceptable and that compound 9g was equipotent to parent 1. These basic urea analogues would be promising leads for the development of novel antitumor agents. |
| تدمد: | 1881-1469 0021-8820 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9dd562559f0e9b8c85df0a6ea6edeed8 https://doi.org/10.1038/ja.2016.166 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9dd562559f0e9b8c85df0a6ea6edeed8 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 18811469 00218820 |
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