Publication: Novel naphthoquinones as potent aromatase inhibitors: Synthesis, anticancer, and in silico studies
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Issued Date
2024-11-15
Resource Type
ISSN
00222860
Scopus ID
2-s2.0-85196273190
Journal Title
Journal of Molecular Structure
Volume
1316
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Molecular Structure Vol.1316 (2024)
Suggested Citation
Leechaisit R., Mahalapbutr P., Suriya U., Prachayasittikul V., Prachayasittikul S., Ruchirawat S., Prachayasittikul V., Pingaew R. Novel naphthoquinones as potent aromatase inhibitors: Synthesis, anticancer, and in silico studies. Journal of Molecular Structure Vol.1316 (2024). doi:10.1016/j.molstruc.2024.138981 Retrieved from: https://hdl.handle.net/20.500.14740/20165
Corresponding Author(s)
Other Contributor(s)
Abstract
A 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.