Epidermal growth factor receptor stimulates tumor growth and progression through several mechanisms. The expression of transcription, mutation, and/or gene amplification may be the cause of EGFR activation in tumor cells. The increased protein and transcribed levels of EGFR will correspond to poor prognosis in several cancers such as lung cancer and colorectal cancer (Allam et al. 2020). The VEGFR has multiple immediate effects on cancer cells and is known to have a major contribution to angiogenesis that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessel formation (Dziobek et al. 2019). LC-HR-MS analysis (Fig. 1S) for dereplication purposes was adopted for the identification of metabolites from ethanol extract of Dictyopteris acrostichoides (Table 1S). The dereplication study of the metabolites against the DNP (Dictionary of Natural Products) (Buckingham 2014) and Marin Lit databases (Munro and Blunt 2023) resulted in the identification of 17 compounds. Ethanol extract of D. acrostichoides as a source of bioactive natural products resulted in the detection of α-dictyopterol (1), β-dictyopterol (2) (Etsuro et al. 1966), germacra-1(10),4(15)-11-trien-5S-ol (3) (Toshi et al. 1964), 4α,5β-dihydroxycubenol (4), cadinan-1,4,5-triol (5) (Qiao et al. 2009), (1R,3R,4S,11R)-3,4;7,8-bisepoxydolabellan-12(18)-ene (6) (Wright et al. 1990), chromenol (7) (Wang et al. 2018), dictyochromenol (8) (Li et al. 2022), isochromazonarol (9), chromazonarol (10), 2-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl] benzene-1,4-diol (11), zonaric acid (12), (Ishibashi et al. 2013), isozonarol (13), zonarol (14) (Fenical et al. 1973), and dictyvaric acid (15) (Song et al. 2005), (3-oxo-undecyldisulfanyl)-undecan-3-one (16) (Schnitzler et al. 1998), and di(3-acetoxy-5-undecenyl) disulfide (17) (Moore et al. 1972) from LC-HR-ESI–MS metabolic profiling of the ethanol extract of D. acrostichoides.

(1R,3R,4S,11R)-3,4;7,8-Bisepoxydolabellan-12(18)-ene (6) is a dolabellane diterpene, typical product of algae of the genus Dictyota (Rushdi et al. 2022b); this mixing (Dictyota and Dictyopteris) must have occurred during the collection process. The cytotoxic potential obtained results revealed that the ethanol extract of D. acrostichoides had promising cytotoxicity activities against HepG2, MCF-7, and Caco-2 cell lines with IC50 values of 11.65, 9.28, and 16.86 µg/ml, respectively, compared to doxorubicin (IC50 5.72, 5.17, and 5.81 µg/ml, respectively); thus, it was further subjected to other assays while other extracts of C. racemosa, H. opuntia, and P. myrica did not show cytotoxic activities against tested cell lines. Further screen of ethanol extract of D. acrostichoides displayed in vitro activity against EGFR (IC50 0.11 µg/ml) compared to lapatinib as a positive control (IC50 0.03 ± 0.002 µg/ml) and against VEGF (IC50 0.276 µg/ml) compared to sorafenib as a positive control (IC50 0.049 ± 0.003 µg/ml). Most compounds showed hydrogen bonding with the gatekeeper mutant Met790. Interestingly, compounds 17 and 16 showed higher docking scores than Gefitinib (Table 2S, Fig. 2S–4S). Compounds (2, 5, 8–15) were of good binding energies ranging from − 6.9734 to − 6.1317 kcal/mol while (1, 3–4, 6–7) were of fair binding energies less than 6 kcal/mol. The docking on VEGFR revealed that most compounds formed hydrogen bonding with Asp 1044 like that of the ligand KIM. Compound 17 has a binding score (− 8.2601 kcal/mol more than ligand KIM (− 7.8176 kcal/mol) while compounds 16 and 12 showed − 7.4368 and − 7.0233 kcal/mol, respectively (Table 3S, Fig. 4S–6S). Compounds 8–13 and 15 showed good binding energies ranging from − 6.8160 to − 6.3920 kcal/mol. Most compounds formed hydrogen bonding with Asp 1044 like that of the ligand KIM.