Publication: Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study
Issued Date
2017-05-16
Resource Type
ISSN
16112156
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2-s2.0-85019633218
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Mahidol University
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SCOPUS
Bibliographic Citation
EXCLI Journal. Vol.16, (2017), 714-726
Suggested Citation
Veda Prachayasittikul, Ratchanok Pingaew, Apilak Worachartcheewan, Somkid Sitthimonchai, Chanin Nantasenamat, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study. EXCLI Journal. Vol.16, (2017), 714-726. doi:10.17179/excli2017-309 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41421
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Title
Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study
Abstract
© 2017, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. A series of 2-amino(chloro)-3-chloro-1,4-naphthoquinone derivatives (1-11) were investigated for their aromatase inhibitory activities. 1,4-Naphthoquinones 1 and 4 were found to be the most potent compounds affording IC50 values 5.2 times lower than the reference drug, ketoconazole. A quantitative structure-activity relationship (QSAR) model provided good predictive performance (R2 CV = 0.9783 and RMSECV = 0.0748) and indicated mass (Mor04m and H8m), electronegativity (Mor08e), van der Waals volume (G1v) and structural information content index (SIC2) descriptors as key descriptors governing the activity. To investigate the effects of structural modifications on aromatase inhibitory activity, the model was employed to predict the activities of an additional set of 39 structurally modified compounds constructed in silico. The prediction suggested that the 2,3-disubstitution of 1,4-naphthoquinone ring with halogen atoms (i.e., Br, I and F) is the most effective modification for potent activity (1a, 1b and 1c). Importantly, compound 1b was predicted to be more potent than its parent compound 1 (11.90-fold) and the reference drug, letrozole (1.03-fold). The study suggests the 1,4-naphthoquinone derivatives as promising compounds to be further developed as a novel class of aromatase inhibitors.