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Title: Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study
Authors: Prachayasittikul V.
Pingaew R.
Worachartcheewan A.
Sitthimonchai S.
Nantasenamat C.
Prachayasittikul S.
Ruchirawat S.
Prachayasittikul V.
Keywords: 1,4 naphthoquinone derivative
2 amino(chloro) 3 chloro 1,4 naphthoquinone derivative
compound 1
compound 10
compound 11
compound 2
compound 3
compound 4
compound 5
compound 6
compound 7
compound 8
compound 9
unclassified drug
computer model
controlled study
drug determination
drug structure
drug synthesis
human cell
quantitative structure activity relation
Issue Date: 2017
Abstract: 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. © 2017, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
ISSN: 16112156
Appears in Collections:Scopus 1983-2021

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