Leechaisit R.Mahalapbutr P.Suriya U.Prachayasittikul V.Prachayasittikul S.Ruchirawat S.Prachayasittikul V.Pingaew R.Mahidol University2024-06-252024-06-252024-11-15Journal of Molecular Structure Vol.1316 (2024)00222860https://repository.li.mahidol.ac.th/handle/20.500.14594/99002A set of 26 naphthoquinone derivatives (3-28) were synthesized by nucleophilic substitution or Michael addition of various amines with 1,4-naphthoquinones and were investigated for their aromatase inhibitory and anticancer activities. The 1,4-naphthoquinone derivatives with amino substituents (14-16 and 24) and the N-alkylated products (25-28) showed promising aromatase inhibitory activity (IC50 = 0.006–2.6 µM). Interestingly, 2-((4-aminophenyl)amino)-3-chloronaphthalene-1,4-dione 14 was noted as a highly potent aromatase inhibitor (IC50 = 6 nM) possessing preferable selective anticancer effect against the breast cancer T47D cell line (IC50: cytotoxic T47D = 24.3 µM, non-cytotoxic to MRC-5 normal cell line, selective index > 6.9). Findings from molecular docking study also suggested that the hydrogen bond formation with Asp309 as well as the pi-sulfur interaction with Met374 residues may be essential for a striking inhibitory effect of the most potent compound 14. Moreover, the in silico drug-likeness prediction indicated that all active naphthoquinone-based compounds are drug-like molecules with potential to be further developed as dual-action anticancer agents for breast cancer management.ChemistryArticleSCOPUS10.1016/j.molstruc.2024.1389812-s2.0-85196273190