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Viruses 2012, 4(8), 1279-1288; doi:10.3390/v4081279
Communication

A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor

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Received: 3 July 2012; in revised form: 7 August 2012 / Accepted: 8 August 2012 / Published: 15 August 2012
(This article belongs to the Special Issue Advances in Filovirus Research 2012)
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Abstract: Ebola (EBOV) and Marburg (MARV) filoviruses are highly infectious pathogens causing deadly hemorrhagic fever in humans and non-human primates. Promising vaccine candidates providing immunity against filoviruses have been reported. However, the sporadic nature and swift progression of filovirus disease underlines the need for the development of small molecule therapeutics providing immediate antiviral effects. Herein we describe a brief structural exploration of two previously reported diazachrysene (DAAC)-based EBOV inhibitors. Specifically, three analogs were prepared to examine how slight substituent modifications would affect inhibitory efficacy and inhibitor-mediated toxicity during not only EBOV, but also MARV cellular infection. Of the three analogs, one was highly efficacious, providing IC50 values of 0.696 µM ± 0.13 µM and 2.76 µM ± 0.21 µM against EBOV and MARV infection, respectively, with little or no associated cellular toxicity. Overall, the structure-activity and structure-toxicity results from this study provide a framework for the future development of DAAC-based filovirus inhibitors that will be both active and non-toxic in vivo.
Keywords: filovirus; Ebola virus; Marburg virus; antiviral; diazachrysene; inhibitory efficacy; toxicity; small molecule filovirus; Ebola virus; Marburg virus; antiviral; diazachrysene; inhibitory efficacy; toxicity; small molecule
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Selaković, Ž.; Opsenica, D.; Eaton, B.; Retterer, C.; Bavari, S.; Burnett, J.C.; Šolaja, B.A.; Panchal, R.G. A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor. Viruses 2012, 4, 1279-1288.

AMA Style

Selaković Ž, Opsenica D, Eaton B, Retterer C, Bavari S, Burnett JC, Šolaja BA, Panchal RG. A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor. Viruses. 2012; 4(8):1279-1288.

Chicago/Turabian Style

Selaković, Života; Opsenica, Dejan; Eaton, Brett; Retterer, Cary; Bavari, Sina; Burnett, James C.; Šolaja, Bogdan A.; Panchal, Rekha G. 2012. "A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor." Viruses 4, no. 8: 1279-1288.



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