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

The phytochemical investigation of the hydromethanolic extract of Carica papaya 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-O-neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3-O-beta-D-gluacopyranoside (9). The compounds 2, 3, 5-7 and 9 were isolated for the first time from the genus Carica. An in vitro breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and ditorin demonstrated the most potent cytotoxic activities with an IC50 of 1.11 +/- 0.06 and 2.47 +/- 0.14 mu M, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR(wt) kinase inhibition activities with an IC50 of 37.3 +/- 1.9 and 41.08 +/- 2.1 nM, respectively, compared with the positive control erlotinib (IC50 = 35.94 +/- 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC50 of 77.41 +/- 4.53 and 92.84 +/- 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC50 = 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(-1) and RMSD value of 1.69 angstrom. Ditorin 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 angstrom. Compounds (1-3) possessed a good bioavallability score with a 0.55 value.

Automated summary

The phytochemical investigation of Carica papaya leaves led to the isolation and characterization of ten compounds. Methyl gallate and clitorin showed potent cytotoxic activities and enzyme inhibitory properties, comparable to standard drugs. Molecular docking simulations demonstrated the binding ability of some compounds to their target receptors.