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- Hamed, A. N. E., et al.
(författare)
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Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking
- 2022
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Ingår i: Rsc Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 12:15, s. 9154-9162
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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