Cornulacin: a new isoflavone from Cornulaca monacantha and its isolation, structure elucidation and cytotoxicity...

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.