Publication: Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study
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Issued Date
2017
Resource Type
File Type
application/pdf
ISSN
16112156
Other identifier(s)
2-s2.0-85019633218
Rights Holder(s)
Scopus
Bibliographic Citation
EXCLI Journal. Vol 16, (2017), p.714-726
Suggested Citation
Prachayasittikul V., Pingaew R., Worachartcheewan A., Sitthimonchai S., Nantasenamat C., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study. EXCLI Journal. Vol 16, (2017), p.714-726. doi:10.17179/excli2017-309 Retrieved from: https://hdl.handle.net/20.500.14740/4161
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.
Subject(s)
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
Doxorubicin
Ketoconazole
Letrozole
Unclassified drug
Article
Computer model
Controlled study
Cytotoxicity
Drug determination
Drug structure
Drug synthesis
Human
Human cell
IC50
Quantitative structure activity relation
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
Doxorubicin
Ketoconazole
Letrozole
Unclassified drug
Article
Computer model
Controlled study
Cytotoxicity
Drug determination
Drug structure
Drug synthesis
Human
Human cell
IC50
Quantitative structure activity relation