naphthoquinones and caffeic-acid-phenethyl-ester

Due to the resistance to drugs, studies involving the combination and controlled release of different agents are gradually increasing. In this study, two different active ingredients, known to have antibacterial and antiparasitic activities, were encapsulated into single polymeric nanoparticles. After co-encapsulation their antibacterial and antileishmanial activity was enhanced approximately 5 and 250 times, respectively. Antibacterial and antileishmanial activities of caffeic acid phenethyl ester and juglone loaded, multifunctional nanoformulations (CJ4-CJ6-CJ8) were also evaluated for the first time in the literature comparatively with their combined free formulations. The antibacterial activity of the multifunctional nanoformulation (CJ8) were found to have a much higher activity (MIC values 6.25 and 12.5 μg ml

Topics: Anti-Bacterial Agents; Antiparasitic Agents; Caffeic Acids; Escherichia coli; Leishmania; Microbial Sensitivity Tests; Nanoparticles; Naphthoquinones; Particle Size; Phenylethyl Alcohol; Polylactic Acid-Polyglycolic Acid Copolymer; Staphylococcus aureus

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi.

Topics: Animals; Antifungal Agents; Biofilms; Caenorhabditis elegans; Caffeic Acids; Candida; Enoxacin; Female; Fluconazole; Intestines; Mice; Mice, Inbred BALB C; Naphthoquinones; NF-kappa B; Phenylethyl Alcohol