K.T Ashitha , S. Lakshmi , S. Anjali , Ajay Krishna , Ved Prakash , Sadasivam Anbumani , S. Priya , Sasidhar B. Somappa
{"title":"设计和发现具有抗三阴性乳腺癌 MDA-MB-231 细胞多方面潜力的羧酰胺基吡唑共轭物","authors":"K.T Ashitha , S. Lakshmi , S. Anjali , Ajay Krishna , Ved Prakash , Sadasivam Anbumani , S. Priya , Sasidhar B. Somappa","doi":"10.1016/j.bmcl.2024.129960","DOIUrl":null,"url":null,"abstract":"<div><p>We report the design, synthesis, and validation of carboxamide-based pyrazole and isoxazole conjugates with a multifaceted activity against Breast Cancer Cell Line MDA-MB-231. The study established that amongst the series, <em>N</em>-(3,5-bis(trifluoromethyl)benzyl)-3-(3,4,5-trimethoxyphenyl)-1<em>H</em>-pyrazole-5-carboxamide (<strong>5</strong><strong>g</strong>) exhibits the highest potency in inhibiting Breast Cancer Cell Line MDA-MB-231 with an IC<sub>50</sub> value of 15.08 ± 0.04 µM. The MDA‐MB‐231 cells, upon treatment with compound <strong>5</strong><strong>g</strong>, exhibited characteristic apoptotic specific activities such as nuclear fragmentation, phosphatidylserine translocation to the outer plasma membrane, release of lactate dehydrogenase (LDH), and upregulation of caspase 3 and caspase 9 activities. Also, the modulation of pro and antiapoptotic proteins in <strong>5</strong><strong>g</strong> treated MDA-MB-231 cells was revealed by membrane array analysis. More importantly, the combination of paclitaxel and compound <strong>5</strong><strong>g</strong> has exhibited improved activity by several folds via their synergistic effects.</p></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"113 ","pages":"Article 129960"},"PeriodicalIF":2.5000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design and discovery of carboxamide-based pyrazole conjugates with multifaceted potential against Triple-Negative Breast cancer MDA-MB-231 cells\",\"authors\":\"K.T Ashitha , S. Lakshmi , S. Anjali , Ajay Krishna , Ved Prakash , Sadasivam Anbumani , S. Priya , Sasidhar B. Somappa\",\"doi\":\"10.1016/j.bmcl.2024.129960\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>We report the design, synthesis, and validation of carboxamide-based pyrazole and isoxazole conjugates with a multifaceted activity against Breast Cancer Cell Line MDA-MB-231. The study established that amongst the series, <em>N</em>-(3,5-bis(trifluoromethyl)benzyl)-3-(3,4,5-trimethoxyphenyl)-1<em>H</em>-pyrazole-5-carboxamide (<strong>5</strong><strong>g</strong>) exhibits the highest potency in inhibiting Breast Cancer Cell Line MDA-MB-231 with an IC<sub>50</sub> value of 15.08 ± 0.04 µM. The MDA‐MB‐231 cells, upon treatment with compound <strong>5</strong><strong>g</strong>, exhibited characteristic apoptotic specific activities such as nuclear fragmentation, phosphatidylserine translocation to the outer plasma membrane, release of lactate dehydrogenase (LDH), and upregulation of caspase 3 and caspase 9 activities. Also, the modulation of pro and antiapoptotic proteins in <strong>5</strong><strong>g</strong> treated MDA-MB-231 cells was revealed by membrane array analysis. More importantly, the combination of paclitaxel and compound <strong>5</strong><strong>g</strong> has exhibited improved activity by several folds via their synergistic effects.</p></div>\",\"PeriodicalId\":256,\"journal\":{\"name\":\"Bioorganic & Medicinal Chemistry Letters\",\"volume\":\"113 \",\"pages\":\"Article 129960\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic & Medicinal Chemistry Letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0960894X24003627\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X24003627","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Design and discovery of carboxamide-based pyrazole conjugates with multifaceted potential against Triple-Negative Breast cancer MDA-MB-231 cells
We report the design, synthesis, and validation of carboxamide-based pyrazole and isoxazole conjugates with a multifaceted activity against Breast Cancer Cell Line MDA-MB-231. The study established that amongst the series, N-(3,5-bis(trifluoromethyl)benzyl)-3-(3,4,5-trimethoxyphenyl)-1H-pyrazole-5-carboxamide (5g) exhibits the highest potency in inhibiting Breast Cancer Cell Line MDA-MB-231 with an IC50 value of 15.08 ± 0.04 µM. The MDA‐MB‐231 cells, upon treatment with compound 5g, exhibited characteristic apoptotic specific activities such as nuclear fragmentation, phosphatidylserine translocation to the outer plasma membrane, release of lactate dehydrogenase (LDH), and upregulation of caspase 3 and caspase 9 activities. Also, the modulation of pro and antiapoptotic proteins in 5g treated MDA-MB-231 cells was revealed by membrane array analysis. More importantly, the combination of paclitaxel and compound 5g has exhibited improved activity by several folds via their synergistic effects.
期刊介绍：
Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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