Authors: | Prachayasittikul, Veda Pingaew, Ratchanok Worachartcheewan, Apilak Sitthimonchai, Somkid Nantasenamat, Chanin Prachayasittikul, Supaluk Ruchirawat, Somsak Prachayasittikul, Virapong |
Title: | Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study |
Language (ISO): | en |
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. |
Subject Headings: | 1,4-naphthoquinones aromatase inhibitory activity structural modification computer-aided drug design anticancer agents |
URI: | http://hdl.handle.net/2003/36157 http://dx.doi.org/10.17877/DE290R-18173 |
Issue Date: | 2017-05-16 |
Rights link: | http://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Original Articles |
Files in This Item:
File | Description | Size | Format | |
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Prachayasittikul_16052017_proof.pdf | DNB | 308.73 kB | Adobe PDF | View/Open |
Prachayasittikul_supplementary_information_16052017.pdf | DNB | 115.72 kB | Adobe PDF | View/Open |
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