Computer modeling approaches to identify new inhibitors are essentially a very sophisticated and efficient way to design drugs. In this study, a bivalent nonpeptide intergrin alpha(v)beta(3) antagonist (bivalent IA) has been synthesized on the basis of an in silico rational design approach. A near-infrared (NIR) fluorescent imaging probe has been developed from this bivalent compound. In vitro binding assays have shown that the bivalent IA (IC(50) = 0.40 +/- 0.11 nM) exhibited improved integrin alpha(v)beta(3) affinity in comparison with the monovalent IA (IC(50) = 22.33 +/- 4.51 nM), resulting in an over 50-fold improvement in receptor affinity. NIR imaging probe, bivalent-IA-Cy5.5 conjugate, also demonstrated significantly increased binding affinity (IC(50) = 0.13 +/- 0.02 nM). Fluorescence microscopy studies showed integrin-mediated endocytosis of bivalent-IA-Cy5.5 in U87 cells which was effectively blocked by nonfluorescent bivalent IA. We also demonstrated tumor accumulation of this NIR imaging probe in U87 mouse xenografts.
Among all novel challenges nowadays worldwide, infectious disease is probably one of the most important. It is wellknown that common treatments used include high doses of antibiotics, which are very invasive therapies for patients. These treatments are more intensive when the infection is related to multidrug resistant microorganisms. In this sense, in this work we report the use of reverse micelles to form less than 5 nm gold, silver, and gold−silver nanoparticles (NPs) with biological activity against five opportunistic Candida strains responsible of several diseases in human beings. As a result, we evaluate the interface properties and droplet−droplet interactions of micelles founding high fluidity in the polar head of the surfactant, necessary to form a flexible interaction channel in the "dimmer" micelle−micelle. In this condition, we form monodispersed, highly reactive NPs with sizes less than 5 nm with high antifungal activity against C. parapsilosis, C. Krusei, C. glabrata, C. guillermondii, and C. albicans, with minimum inhibitory concentrations (MIC 50 ) less than 0.7 ppm in all cases, the lowest reported to the best of our knowledge. These are very promising results to develop alternative therapies to treat fungal diseases in humans, animals, and plants, or to coat conventional surfaces in surgery rooms.
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