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

• Published in: RSC advances 2022-03, Vol.12 (15), p.9154-9162
• Main Authors: Hamed, Ashraf N. E, Abouelela, Mohamed E, El Zowalaty, Ahmed E, Badr, Mohamed M, Abdelkader, Mohamed S. A
• Format: Article
• ISSN: 2046-2069
• DOI: 10.1039/d1ra07000b

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 -β- d -glucopyranoside ( 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 clitorin demonstrated the most potent cytotoxic activities with an IC 50 of 1.11 ± 0.06 and 2.47 ± 0.14 μM, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR wt kinase inhibition activities with an IC 50 of 37.3 ± 1.9 and 41.08 ± 2.1 nM, respectively, compared with the positive control erlotinib (IC 50 = 35.94 ± 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC 50 of 77.41 ± 4.53 and 92.84 ± 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC 50 = 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 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. The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds.