(5R)-丁香烯内酯及其类似物的合成及抗增殖活性研究

IF 1 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Journal of The Serbian Chemical Society Pub Date : 2023-01-01 DOI:10.2298/jsc230126018f
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引用次数: 0

摘要

(5R)-Cleistenolide和一些相关的类似物已经从d-葡萄糖开始合成。合成的关键步骤包括z选择性Wittig烯化和分子内C-5位构型反转的Mitsunobu反应。合成化合物的体外抗增殖活性在8个人类肿瘤细胞组和单个正常细胞系(MRC-5)上进行了测试。大多数被测试的化合物对某些人类肿瘤细胞有很强的抗增殖作用,对正常胎儿肺成纤维细胞(MRC-5)的毒性均可忽略不计。本研究获得的活性最高的化合物是内酯5,其在MDA-MB 231细胞培养中与阿霉素具有相同的活性(IC50为0.09 μ M)。类似物2、5和6在K562细胞株中具有较强的抗增殖活性(IC50分别为0.21、0.34和0.33 μ M),与阿霉素的IC50非常接近(IC50为0.25 μ M)。一项进行的SAR研究表明,在C-5位置的立体化学变化可能会增加所产生的立体异构体的活性。
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Synthesis and antiproliferative activity of (5R)-cleistenolide and analogues
(5R)-Cleistenolide and a few related analogues have been synthesized starting from d-glucose. The key steps of the synthesis included a Z-selective Wittig olefination and an intramolecular Mitsunobu reaction with an inversion of configuration at the C-5 position. In vitro antiproliferative activity of synthesized compounds was tested on a panel of eight human tumour cells and against a single normal cell line (MRC-5). The majority of tested compounds showed strong antiproliferative effects on certain human tumour cells and all of them showed negligible toxicity to normal foetal lung fibroblasts (MRC-5). The most active compound obtained in this work is lactone 5, which in MDA-MB 231 cell culture showed the same activity as doxorubicin (IC50 0.09 ?M). Strong antiproliferative activities of analogues 2, 5 and 6 were recorded in the K562 cell line (IC50 0.21, 0.34 and 0.33 ?M, respectively), in which they showed very similar activities to doxorubicin (IC50 0.25 ?M). A performed SAR study revealed that a change in the stereochemistry at the C-5 position may increase the activity of resulting stereoisomers.
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来源期刊
CiteScore
1.80
自引率
0.00%
发文量
76
审稿时长
1 months
期刊介绍: The Journal of the Serbian Chemical Society -JSCS (formerly Glasnik Hemijskog društva Beograd) publishes articles original papers that have not been published previously, from the fields of fundamental and applied chemistry: Theoretical Chemistry, Organic Chemistry, Biochemistry and Biotechnology, Food Chemistry, Technology and Engineering, Inorganic Chemistry, Polymers, Analytical Chemistry, Physical Chemistry, Spectroscopy, Electrochemistry, Thermodynamics, Chemical Engineering, Textile Engineering, Materials, Ceramics, Metallurgy, Geochemistry, Environmental Chemistry, History of and Education in Chemistry.
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