Yaju Wu, Lin Huang, Xianli Ma, Xiaoqun Zhou, Qian Li and Fangyao Li
{"title":"新型脱氢松香酸-1,2,3-三唑-噁唑烷酮杂交化合物的设计、合成和抗增殖性评价","authors":"Yaju Wu, Lin Huang, Xianli Ma, Xiaoqun Zhou, Qian Li and Fangyao Li","doi":"10.1039/D3MD00550J","DOIUrl":null,"url":null,"abstract":"<p >A series of novel dehydroabietic acid derivatives containing both 1,2,3-triazole and oxazolidinone <strong>4a–4t</strong> have been synthesized and their antiproliferative activity <em>in vitro</em> against HeLa, HepG2, MGC-803 and T-24 cell lines evaluated. Most of them displayed cell proliferation inhibition on four tested human malignant tumour cell lines to some degree. Among them, compound <strong>4p</strong> exhibited promising cytotoxicity with IC<small><sub>50</sub></small> values ranging from 3.18 to 25.31 μM and weak cytotoxicity toward normal cells. The mechanism of action of <strong>4p</strong> was then studied using flow cytometry, Hoechst 33258 staining, ROS generation assay, and JC-1 mitochondrial membrane potential staining, which illustrated that compound <strong>4p</strong> induced apoptosis, arrested mitotic process at the G1 phase of the cell cycle, reduced the mitochondrial membrane potential, and increased intracellular ROS levels. In summary, the introduction of an oxazolidinone group <em>via</em> a “1,2,3-triazole” linker significantly improved the antitumor activity of dehydroabietic acid, and deserves to be further investigated.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":null,"pages":null},"PeriodicalIF":3.5970,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis, and antiproliferative evaluation of novel dehydroabietic acid-1,2,3-triazole-oxazolidinone hybrids†\",\"authors\":\"Yaju Wu, Lin Huang, Xianli Ma, Xiaoqun Zhou, Qian Li and Fangyao Li\",\"doi\":\"10.1039/D3MD00550J\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >A series of novel dehydroabietic acid derivatives containing both 1,2,3-triazole and oxazolidinone <strong>4a–4t</strong> have been synthesized and their antiproliferative activity <em>in vitro</em> against HeLa, HepG2, MGC-803 and T-24 cell lines evaluated. Most of them displayed cell proliferation inhibition on four tested human malignant tumour cell lines to some degree. Among them, compound <strong>4p</strong> exhibited promising cytotoxicity with IC<small><sub>50</sub></small> values ranging from 3.18 to 25.31 μM and weak cytotoxicity toward normal cells. The mechanism of action of <strong>4p</strong> was then studied using flow cytometry, Hoechst 33258 staining, ROS generation assay, and JC-1 mitochondrial membrane potential staining, which illustrated that compound <strong>4p</strong> induced apoptosis, arrested mitotic process at the G1 phase of the cell cycle, reduced the mitochondrial membrane potential, and increased intracellular ROS levels. In summary, the introduction of an oxazolidinone group <em>via</em> a “1,2,3-triazole” linker significantly improved the antitumor activity of dehydroabietic acid, and deserves to be further investigated.</p>\",\"PeriodicalId\":88,\"journal\":{\"name\":\"MedChemComm\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5970,\"publicationDate\":\"2024-01-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"MedChemComm\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/md/d3md00550j\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"MedChemComm","FirstCategoryId":"1085","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/md/d3md00550j","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
Design, synthesis, and antiproliferative evaluation of novel dehydroabietic acid-1,2,3-triazole-oxazolidinone hybrids†
A series of novel dehydroabietic acid derivatives containing both 1,2,3-triazole and oxazolidinone 4a–4t have been synthesized and their antiproliferative activity in vitro against HeLa, HepG2, MGC-803 and T-24 cell lines evaluated. Most of them displayed cell proliferation inhibition on four tested human malignant tumour cell lines to some degree. Among them, compound 4p exhibited promising cytotoxicity with IC50 values ranging from 3.18 to 25.31 μM and weak cytotoxicity toward normal cells. The mechanism of action of 4p was then studied using flow cytometry, Hoechst 33258 staining, ROS generation assay, and JC-1 mitochondrial membrane potential staining, which illustrated that compound 4p induced apoptosis, arrested mitotic process at the G1 phase of the cell cycle, reduced the mitochondrial membrane potential, and increased intracellular ROS levels. In summary, the introduction of an oxazolidinone group via a “1,2,3-triazole” linker significantly improved the antitumor activity of dehydroabietic acid, and deserves to be further investigated.
期刊介绍:
Research and review articles in medicinal chemistry and related drug discovery science; the official journal of the European Federation for Medicinal Chemistry.
In 2020, MedChemComm will change its name to RSC Medicinal Chemistry. Issue 12, 2019 will be the last issue as MedChemComm.