Cornulacin: a new isoflavone from Cornulaca monacantha and its isolation, structure elucidation and cytotoxicity through EGFR-mediated apoptosis†

IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RSC medicinal chemistry Pub Date : 2024-08-22 DOI:10.1039/D4MD00524D
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
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Abstract

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.

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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。
对采集自埃及北西奈半岛的一年生野生草本植物 Cornulaca monacantha(马齿苋科)的甲醇提取物进行化学研究,发现了一种新的异黄酮 cornulacin 1 和五种已知化合物:N-trans-feruloyltyramine 2、N-trans-feruloyl-3'-methoxytyramine 3、N-trans-caffeoyl tyramine 4、Cannabisin F 5 和 (2aS, 3aS) lyciumamide D 6。利用 MTT 试验评估了分离出的化合物对胰腺癌(Panc1)和卵巢癌(A2780)细胞株的体外细胞毒性。化合物 1、2、3 和 4 对测试细胞表现出了良好的细胞毒性活性,其中化合物 1(IC50 为 2.1 ± 0.21 μM)对 A2780 细胞的活性最高,而化合物 2(IC50 为 3.4 ± 0.11 μM)则是对 Panc1 细胞最有效的化合物。因此,利用附件素 V/PI 染色法进一步研究了化合物 1 在 A2780 癌细胞中的凋亡诱导作用。化合物 1 能使卵巢 A2780 癌细胞的凋亡率提高 45.9 倍,并使细胞增殖停止在 S 期。这种活性是通过上调促凋亡基因 Bax、P53、caspase 3、8 和 9 以及下调抗凋亡基因 Bcl-2 来介导的。此外,分子对接研究表明化合物 1 与表皮生长因子受体活性位点有很强的结合亲和力,这验证了其实验性表皮生长因子受体酶抑制活性。
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CiteScore
5.80
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2.40%
发文量
129
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