Badawy Ahmed M, Eltamany Enas E, Hussien Rodina M, Mohamed Osama G, El-Ayouty Mayada M, Nafie Mohamed S, Tripathi Ashootosh, Ahmed Safwat A
Department of Pharmacognosy, Faculty of Pharmacy, Sinai University - Arish Branch Arish 45511 Egypt
Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt
RSC Med Chem. 2024 Aug 22;15(9):3228-38. doi: 10.1039/d4md00524d.
Chemical investigation of the methanolic extract of (Amaranthaceae), an annual wild herb collected from North Sinai, Egypt, yielded a new isoflavone cornulacin 1 and five known compounds: -feruloyltyramine 2, -feruloyl-3'-methoxytyramine 3, -caffeoyl tyramine 4, Cannabisin F 5 and (2a, 3a) lyciumamide D 6. Using MTT assay, the isolated compounds were evaluated for their 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 (IC of 2.1 ± 0.21 μM) was the most active one against A2780 cells, whereas compound 2 (IC 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.
对采自埃及北西奈的一年生野生草本植物（苋科）甲醇提取物进行化学研究，得到一种新的异黄酮玉米黄素1和五种已知化合物：对香豆酰酪胺2、对香豆酰-3'-甲氧基酪胺3、咖啡酰酪胺4、大麻素F 5和(2a, 3a)枸杞酰胺D 6。采用MTT法评估分离得到的化合物对胰腺癌细胞（Panc1）和卵巢癌细胞（A2780）的细胞毒性。化合物1、2、3和4对受试细胞表现出有前景的细胞毒性活性，其中化合物1（IC50为2.1±0.21 μM）对A2780细胞活性最强，而化合物2（IC50为3.4±0.11 μM）对Panc1细胞最有效。因此，使用膜联蛋白V/碘化丙啶染色进一步研究化合物1对A2780癌细胞的凋亡诱导作用。化合物1显著刺激凋亡的卵巢A2780癌细胞达45.9倍，并使细胞增殖停滞在S期。这种活性是通过上调促凋亡基因Bax、P53以及半胱天冬酶3、8和9，同时下调抗凋亡基因Bcl-2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（EGFR）活性位点具有很强的结合亲和力，这验证了其对EGFR酶的实验抑制活性。
