Aromatase inhibitory, anti-proliferative, and apoptosis-inducing effects of naphthoquinone-triazole derivatives for potential anti-breast cancer agents: In vitro and molecular docking studies
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Issued Date
2026-06-04
Resource Type
ISSN
0006291X
eISSN
10902104
Scopus ID
2-s2.0-105034642772
Journal Title
Biochemical and Biophysical Research Communications
Volume
816
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications Vol.816 (2026)
Suggested Citation
Punpai S., Mahalapbutr P., Leechaisit R., Win K.S., Prachayasittikul V., Tanechpongtamb W., Prachayasittikul S., Ruchirawat S., Prachayasittikul V., Pingaew R. Aromatase inhibitory, anti-proliferative, and apoptosis-inducing effects of naphthoquinone-triazole derivatives for potential anti-breast cancer agents: In vitro and molecular docking studies. Biochemical and Biophysical Research Communications Vol.816 (2026). doi:10.1016/j.bbrc.2026.153683 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116073
Title
Aromatase inhibitory, anti-proliferative, and apoptosis-inducing effects of naphthoquinone-triazole derivatives for potential anti-breast cancer agents: In vitro and molecular docking studies
Corresponding Author(s)
Other Contributor(s)
Abstract
Aromatase enzyme is a rate-limiting enzyme playing a key role in estrogen biosynthesis, and its inhibition has been noted as a strategy for the management of hormone-dependent breast cancers. Naphthoquinone and triazole are attractive pharmacophores due to their wide-ranging bioactivities and unique chemical properties. Molecular hybridization is a strategy widely applied in drug design to create several novel compounds with promising therapeutic advantages. In this study, a series of hybridized naphthoquinone-triazoles (1–17) were investigated for their aromatase inhibitory effects. Twelve compounds were found to be active aromatase inhibitors (IC<inf>50</inf> = 1.3–14.9 μM). Molecular docking was conducted to reveal that the three most potent inhibitors (2, 5, and 7, IC<inf>50</inf> = 1.3–1.8 μM) could occupy the allosteric binding site of human aromatase. These three most potent inhibitors (2, 5, and 7) were further explored for their antiproliferative and apoptosis-inducing activities against the estrogen-positive MCF-7 breast cancer cell line. Interestingly, these three aromatase inhibitors exhibited antiproliferative activity (IC<inf>50</inf> = 17.51–36.54 μM) and apoptosis-inducing effects, as observed by increased levels of the cell accumulated in the sub-G1 phase. Notably, methyl derivative 2 outperformed the other derivatives with its comparable potency (IC<inf>50</inf> = 17.51, SI = 4.60) and higher selectivity index than the standard drug, tamoxifen (IC<inf>50</inf> = 18.11, SI = 1.56). Collectively, this study suggested that these naphthoquinone-triazole derivatives were aromatase inhibitors possessing the apoptosis-inducing effect, which could be further developed as multi-acting anticancer agents for combating estrogen-dependent breast cancer.