Ahmed M. Badawy, Enas E. Eltamany, Rodina M. Hussien, Osama G. Mohamed, Mayada M. El-Ayouty, Mohamed S. Nafie, Ashootosh Tripathi and Safwat A. Ahmed
{"title":"山茱萸素:从山茱萸中提取的一种新异黄酮及其分离、结构阐明和通过表皮生长因子受体介导的细胞凋亡产生的细胞毒性。","authors":"Ahmed M. Badawy, Enas E. Eltamany, Rodina M. Hussien, Osama G. Mohamed, Mayada M. El-Ayouty, Mohamed S. Nafie, Ashootosh Tripathi and Safwat A. Ahmed","doi":"10.1039/D4MD00524D","DOIUrl":null,"url":null,"abstract":"<p >Chemical investigation of the methanolic extract of <em>Cornulaca monacantha</em> (Amaranthaceae), an annual wild herb collected from North Sinai, Egypt, yielded a new isoflavone cornulacin <strong>1</strong> and five known compounds: <em>N-trans</em>-feruloyltyramine <strong>2</strong>, <em>N-trans</em>-feruloyl-3′-methoxytyramine <strong>3</strong>, <em>N-trans</em>-caffeoyl tyramine <strong>4</strong>, Cannabisin F <strong>5</strong> and (2a<em>S</em>, 3a<em>S</em>) lyciumamide D <strong>6</strong>. Using MTT assay, the isolated compounds were evaluated for their <em>in vitro</em> cytotoxicity against pancreatic (Panc1) and ovarian (A2780) cancer cell lines. Compounds <strong>1</strong>, <strong>2</strong>, <strong>3</strong>, and <strong>4</strong> exhibited promising cytotoxic activity against the tested cells, among which compound <strong>1</strong> (IC<small><sub>50</sub></small> of 2.1 ± 0.21 μM) was the most active one against A2780 cells, whereas compound <strong>2</strong> (IC<small><sub>50</sub></small> of 3.4 ± 0.11 μM) was the most effective compound against Panc1 cells. Accordingly, compound <strong>1</strong> was further investigated for its apoptotic induction in A2780 cancer cells using Annexin V/PI staining. Compound <strong>1</strong> significantly stimulated apoptotic ovarian A2780 cancer cells by 45.9-fold and arrested cell proliferation in the S-phase. Such activity was mediated through the upregulation of proapoptotic genes Bax; P53; and caspase 3, 8, and 9 besides the downregulation of the Bcl-2 gene, the anti-apoptotic one. Furthermore, molecular docking investigation demonstrated the strong binding affinity of compound <strong>1</strong> with EGFR active sites, which validated its experimental EGFR enzyme inhibition activity.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 9","pages":" 3228-3238"},"PeriodicalIF":4.1000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cornulacin: a new isoflavone from Cornulaca monacantha and its isolation, structure elucidation and cytotoxicity through EGFR-mediated apoptosis†\",\"authors\":\"Ahmed M. Badawy, Enas E. Eltamany, Rodina M. Hussien, Osama G. Mohamed, Mayada M. El-Ayouty, Mohamed S. Nafie, Ashootosh Tripathi and Safwat A. Ahmed\",\"doi\":\"10.1039/D4MD00524D\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Chemical investigation of the methanolic extract of <em>Cornulaca monacantha</em> (Amaranthaceae), an annual wild herb collected from North Sinai, Egypt, yielded a new isoflavone cornulacin <strong>1</strong> and five known compounds: <em>N-trans</em>-feruloyltyramine <strong>2</strong>, <em>N-trans</em>-feruloyl-3′-methoxytyramine <strong>3</strong>, <em>N-trans</em>-caffeoyl tyramine <strong>4</strong>, Cannabisin F <strong>5</strong> and (2a<em>S</em>, 3a<em>S</em>) lyciumamide D <strong>6</strong>. Using MTT assay, the isolated compounds were evaluated for their <em>in vitro</em> cytotoxicity against pancreatic (Panc1) and ovarian (A2780) cancer cell lines. Compounds <strong>1</strong>, <strong>2</strong>, <strong>3</strong>, and <strong>4</strong> exhibited promising cytotoxic activity against the tested cells, among which compound <strong>1</strong> (IC<small><sub>50</sub></small> of 2.1 ± 0.21 μM) was the most active one against A2780 cells, whereas compound <strong>2</strong> (IC<small><sub>50</sub></small> of 3.4 ± 0.11 μM) was the most effective compound against Panc1 cells. Accordingly, compound <strong>1</strong> was further investigated for its apoptotic induction in A2780 cancer cells using Annexin V/PI staining. Compound <strong>1</strong> significantly stimulated apoptotic ovarian A2780 cancer cells by 45.9-fold and arrested cell proliferation in the S-phase. Such activity was mediated through the upregulation of proapoptotic genes Bax; P53; and caspase 3, 8, and 9 besides the downregulation of the Bcl-2 gene, the anti-apoptotic one. Furthermore, molecular docking investigation demonstrated the strong binding affinity of compound <strong>1</strong> with EGFR active sites, which validated its experimental EGFR enzyme inhibition activity.</p>\",\"PeriodicalId\":21462,\"journal\":{\"name\":\"RSC medicinal chemistry\",\"volume\":\" 9\",\"pages\":\" 3228-3238\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RSC medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/md/d4md00524d\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/md/d4md00524d","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Cornulacin: a new isoflavone from Cornulaca monacantha and its isolation, structure elucidation and cytotoxicity through EGFR-mediated apoptosis†
Chemical investigation of the methanolic extract of Cornulaca monacantha (Amaranthaceae), an annual wild herb collected from North Sinai, Egypt, yielded a new isoflavone cornulacin 1 and five known compounds: N-trans-feruloyltyramine 2, N-trans-feruloyl-3′-methoxytyramine 3, N-trans-caffeoyl tyramine 4, Cannabisin F 5 and (2aS, 3aS) lyciumamide D 6. Using MTT assay, the isolated compounds were evaluated for their in vitro cytotoxicity against pancreatic (Panc1) and ovarian (A2780) cancer cell lines. Compounds 1, 2, 3, and 4 exhibited promising cytotoxic activity against the tested cells, among which compound 1 (IC50 of 2.1 ± 0.21 μM) was the most active one against A2780 cells, whereas compound 2 (IC50 of 3.4 ± 0.11 μM) was the most effective compound against Panc1 cells. Accordingly, compound 1 was further investigated for its apoptotic induction in A2780 cancer cells using Annexin V/PI staining. Compound 1 significantly stimulated apoptotic ovarian A2780 cancer cells by 45.9-fold and arrested cell proliferation in the S-phase. Such activity was mediated through the upregulation of proapoptotic genes Bax; P53; and caspase 3, 8, and 9 besides the downregulation of the Bcl-2 gene, the anti-apoptotic one. Furthermore, molecular docking investigation demonstrated the strong binding affinity of compound 1 with EGFR active sites, which validated its experimental EGFR enzyme inhibition activity.