Chemical constituents from Linn. leaves as potential cytotoxic, EGFR and aromatase (CYP19A) inhibitors; a study supported by molecular docking.

The phytochemical investigation of the hydromethanolic extract of Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3--neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3--β-d-glucopyranoside (9). The compounds 2, 3, 5-7 and 9 were isolated for the first time from the genus . An breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and clitorin demonstrated the most potent cytotoxic activities with an IC of 1.11 ± 0.06 and 2.47 ± 0.14 μM, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR kinase inhibition activities with an IC of 37.3 ± 1.9 and 41.08 ± 2.1 nM, respectively, compared with the positive control erlotinib (IC = 35.94 ± 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC of 77.41 ± 4.53 and 92.84 ± 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC = 77.72 ± 4.55). Additionally, molecular docking simulations of the isolated compounds to EGFR and human placental aromatase cytochrome P450 (CYP19A1) were evaluated. Methyl gallate linked with the EGFR receptor through hydrogen bonding with a pose score of -4.5287 kcal mol and RMSD value of 1.69 Å. Clitorin showed the strongest interaction with aromatase (CYP19A1) for the breast cancer receptor with a posing score of -14.2074 and RMSD value of 1.56 Å. Compounds (1-3) possessed a good bioavailability score with a 0.55 value.