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Kathryn K. Najafi, Andreas Jekle, Dmitri Debabov, Steve Wilmarth, Rakesh Jain, Chris Celeri, Meghan Zuck, Timothy Shiau, Eddy Low, Anderson Mark; Aganocide Compounds Effective Against Ophthalmic Pathogens. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2063.
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© ARVO (1962-2015); The Authors (2016-present)
There is no effective medication for adenoviral conjunctivitis currently available. Novel treatment options are needed that would target both the viral and bacterial etiological agents of conjunctivitis. In this report, we show results on Aganocide compounds, a new class of topical microbicides with in vitro efficacy against common ophthalmic pathogens such as Adenovirus, Herpes Simplex Virus, S. aureus, S. marcescens, H. influenzae and C. albicans.
The microbicidal effect of Aganocide compounds was tested in modified minimal bactericidal or fungicidal concentration and time-kill assays. Viral titer reduction assays as well as dose- and time-dependency experiments were used to determine the virucidal activity. Cytotoxic profiles were measured on mouse L929 fibroblasts.
We have shown that our first-in-class Aganocide compound, NVC-422 (2-(dichloroamino)-2-methylpropanesulfonic acid), has broad-spectrum activity against viral, bacterial and fungal ocular pathogens. Here, we present new Aganocide compounds with increased virucidal, bactericidal or fungicidal activity, more favorable cytotoxicity profile or pH-independent activity. NVC-638 (2-(3-(dichloroamino)-3-methylbutylsulfonyl)ethanesulfonic acid) has similar microbicidal activity but a further improved cytotoxicity profile compared to NVC-422. The acyclic hydrophilic compound NVC-727 (3-(3-(dichloroamino)-3-methylbutylsulfonyl)propane-1,2-diol) has better anti-HSV-1 and bactericidal activity over a broad pH range while maintaining the excellent anti-Adenovirus activity of NVC-422. Finally, the cyclic compound NVC-704 (3-(3-chloro-2,2,4,4-tetramethyl-5-oxoimidazolidin-1-yl)propane-1-sulfonic acid) has increased activity against C. albicans combined with a favorable cytotoxicity, bactericidal and virucidal profile.
We present novel, fast-acting, broad-spectrum Aganocide compounds with good solution stability and broad-spectrum activity against viral, bacterial and fungal ophthalmic pathogens. The broad-spectrum in vitro activity and good cytotoxicity profile validate Aganocide compounds as new therapeutic agents for the treatment of both viral and bacterial conjunctivitis.
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