{"title":"人工合成的 Kusunokinin 类似物对人类癌细胞株的抗癌活性","authors":"Patpanat Sermmai , Kornthip Tangthana-umrung , Anawat Tailangka , Thidarath Rattanaburee , Chompunud Chompunud Na Ayudhya , Kulvadee Dolsophon , Varomyalin Tipmanee , Potchanapond Graidist , Tienthong Thongpanchang","doi":"10.1016/j.tet.2024.134362","DOIUrl":null,"url":null,"abstract":"<div><div>The series of racemic kusunokinin derivatives were synthesized and their cytotoxic activities and cell viability on cancer cells including breast cancer (MCF-7, MDA-MB468), colon cancer (HT-29), cholangiocarcinoma (KKU-M213) and ovarian cancer (A2780) cells were investigated. The results showed that compounds <strong>6aa</strong>, <strong>6da</strong>, and <strong>6de</strong> exhibited growth inhibition against breast cancer (MDA-MB468), cholangiocarcinoma (KKU-M213), colon cancer (HT-29), and ovarian cancer (A2780) cells with IC50 values (<em>μ</em>M) 13.77 ± 0.38, 7.94 ± 0.45, and 4.22 ± 0.13 (MDA-MB468); 4.21 ± 0.21, 0.97 ± 0.03, and 0.09 ± 0.02 (KKU-M213); 22.66 ± 0.23, and 15.62 ± 0.06 (HT-29); 13.11 ± 0.37, 11.51 ± 0.43, and 1.87 ± 0.01 (A2780); respectively. Interestingly, a positive control, doxorubicin, showed less cytotoxicity than <strong>6da</strong> and <strong>6de</strong> on cholangiocarcinoma KKU-M213 and ovarian cancer A2780 cells. Moreover, these three synthetic compounds also exhibited less toxicity than doxorubicin on the normal cells, MMNK-1, Vero and L-929. The binding possibility towards CSF1R, <strong>6de</strong> (−11.59 kcal/mol) and <em>trans</em>-(−)-kusunokinin (−11.75 kcal/mol) were similar in both docking energies and docking poses. <strong>6de</strong> interacted with Trp550 <em>via</em> π-π stacking in the similar manner with <em>trans</em>-(−)-kusunokinin and <em>trans</em>-(+)-kusunokinin.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"170 ","pages":"Article 134362"},"PeriodicalIF":2.1000,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anticancer activity of the synthetic kusunokinin analogues on human cancer cell lines\",\"authors\":\"Patpanat Sermmai , Kornthip Tangthana-umrung , Anawat Tailangka , Thidarath Rattanaburee , Chompunud Chompunud Na Ayudhya , Kulvadee Dolsophon , Varomyalin Tipmanee , Potchanapond Graidist , Tienthong Thongpanchang\",\"doi\":\"10.1016/j.tet.2024.134362\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The series of racemic kusunokinin derivatives were synthesized and their cytotoxic activities and cell viability on cancer cells including breast cancer (MCF-7, MDA-MB468), colon cancer (HT-29), cholangiocarcinoma (KKU-M213) and ovarian cancer (A2780) cells were investigated. The results showed that compounds <strong>6aa</strong>, <strong>6da</strong>, and <strong>6de</strong> exhibited growth inhibition against breast cancer (MDA-MB468), cholangiocarcinoma (KKU-M213), colon cancer (HT-29), and ovarian cancer (A2780) cells with IC50 values (<em>μ</em>M) 13.77 ± 0.38, 7.94 ± 0.45, and 4.22 ± 0.13 (MDA-MB468); 4.21 ± 0.21, 0.97 ± 0.03, and 0.09 ± 0.02 (KKU-M213); 22.66 ± 0.23, and 15.62 ± 0.06 (HT-29); 13.11 ± 0.37, 11.51 ± 0.43, and 1.87 ± 0.01 (A2780); respectively. Interestingly, a positive control, doxorubicin, showed less cytotoxicity than <strong>6da</strong> and <strong>6de</strong> on cholangiocarcinoma KKU-M213 and ovarian cancer A2780 cells. Moreover, these three synthetic compounds also exhibited less toxicity than doxorubicin on the normal cells, MMNK-1, Vero and L-929. The binding possibility towards CSF1R, <strong>6de</strong> (−11.59 kcal/mol) and <em>trans</em>-(−)-kusunokinin (−11.75 kcal/mol) were similar in both docking energies and docking poses. <strong>6de</strong> interacted with Trp550 <em>via</em> π-π stacking in the similar manner with <em>trans</em>-(−)-kusunokinin and <em>trans</em>-(+)-kusunokinin.</div></div>\",\"PeriodicalId\":437,\"journal\":{\"name\":\"Tetrahedron\",\"volume\":\"170 \",\"pages\":\"Article 134362\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-11-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tetrahedron\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S004040202400543X\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tetrahedron","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S004040202400543X","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Anticancer activity of the synthetic kusunokinin analogues on human cancer cell lines
The series of racemic kusunokinin derivatives were synthesized and their cytotoxic activities and cell viability on cancer cells including breast cancer (MCF-7, MDA-MB468), colon cancer (HT-29), cholangiocarcinoma (KKU-M213) and ovarian cancer (A2780) cells were investigated. The results showed that compounds 6aa, 6da, and 6de exhibited growth inhibition against breast cancer (MDA-MB468), cholangiocarcinoma (KKU-M213), colon cancer (HT-29), and ovarian cancer (A2780) cells with IC50 values (μM) 13.77 ± 0.38, 7.94 ± 0.45, and 4.22 ± 0.13 (MDA-MB468); 4.21 ± 0.21, 0.97 ± 0.03, and 0.09 ± 0.02 (KKU-M213); 22.66 ± 0.23, and 15.62 ± 0.06 (HT-29); 13.11 ± 0.37, 11.51 ± 0.43, and 1.87 ± 0.01 (A2780); respectively. Interestingly, a positive control, doxorubicin, showed less cytotoxicity than 6da and 6de on cholangiocarcinoma KKU-M213 and ovarian cancer A2780 cells. Moreover, these three synthetic compounds also exhibited less toxicity than doxorubicin on the normal cells, MMNK-1, Vero and L-929. The binding possibility towards CSF1R, 6de (−11.59 kcal/mol) and trans-(−)-kusunokinin (−11.75 kcal/mol) were similar in both docking energies and docking poses. 6de interacted with Trp550 via π-π stacking in the similar manner with trans-(−)-kusunokinin and trans-(+)-kusunokinin.
期刊介绍：
Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry.
Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters.
Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.
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