Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study

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dc.contributor.authorPrachayasittikul, Veda
dc.contributor.authorPingaew, Ratchanok
dc.contributor.authorWorachartcheewan, Apilak
dc.contributor.authorSitthimonchai, Somkid
dc.contributor.authorNantasenamat, Chanin
dc.contributor.authorPrachayasittikul, Supaluk
dc.contributor.authorRuchirawat, Somsak
dc.contributor.authorPrachayasittikul, Virapong
dc.date.accessioned2017-10-27T12:16:02Z
dc.date.available2017-10-27T12:16:02Z
dc.date.issued2017-05-16
dc.description.abstractA 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.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/36157
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-18173
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal;Vol. 16 2017
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject1,4-naphthoquinonesen
dc.subjectaromatase inhibitory activityen
dc.subjectstructural modificationen
dc.subjectcomputer-aided drug designen
dc.subjectanticancer agentsen
dc.subject.ddc610
dc.titleAromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR studyen
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.secondarypublicationtrue

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