02917nas a2200313   4500008004100000022001400041245008300055210006900138260007300207300001400280490000900294520181400303653002302117653003202140653001402172653002102186653003402207100002702241700002802268700002002296700002502316700002202341700002402363700002602387700002602413700002102439700002902460856011402489       2013                        eng d  a0304-416500aMechanism of action of novel synthetic dodecapeptides against Candida albicans0 aMechanism of action of novel synthetic dodecapeptides against Ca  aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcNOV  a5193-52030 v18303 a<p>Background: Three de novo designed low molecular weight cationic peptides (IJ2, IJ3 and IJ4) containing an unnatural amino acid alpha,beta-didehydrophenylalanine (APhe) exhibited potent antifungal activity against fluconazole (FLC) sensitive and resistant clinical isolates of Candida albicans as well as non-albi cans and other yeast and filamentous pathogenic fungi. In the present study, their synthesis, susceptibility of different fungi and the mechanism of anti-candidal action have been elucidated. Methods: The antimicrobial peptides (AMPs) were synthesized by solid-phase method and checked for antifungal activity against different yeasts and fungi by broth microdilution method. Anti-candidal mode of action of the peptides was investigated through detecting membrane permeabilization by confocal microscopy, Reactive Oxygen Species (ROS) generation by fluorometry, apoptosis and necrosis by flow cytometry and cell wall damage using Scanning and Transmission Electron Microscopy. Results and conclusions: The MIC of the peptides against C. albicans and other yeast and filamentous fungal pathogens ranged between 3.91 and 250 mu M. All three peptides exhibited effect on multiple targets in C. albi cans including disruption of cell wall structures, compromised cell membrane permeability leading to their enhanced entry into the cells, accumulation of ROS and induction of apoptosis. The peptides also showed synergistic effect when used in combination with fluconazole (FLC) and caspofungin (CAS) against C. albi cans. General significance: The study suggests that the AMPs alone or in combination with conventional antifungals hold promise for the control of fungal pathogens, and need to be further explored for treatment of fungal infections. (C) 2013 Elsevier By. All rights reserved.</p>10aAntifungal peptide10aAntimicrobial peptide (AMP)10aApoptosis10aCandida albicans10aReactive Oxygen Species (ROS)1 aMaurya, Indresh, Kumar1 aThota, Chaitanya, Kumar1 aSharma, Jyotsna1 aTupe, Santosh, Genba1 aChaudhary, Preeti1 aSingh, Manoj, Kumar1 aThakur, Indu, Shekhar1 aDeshpande, Mukund, V.1 aPrasad, Rajendra1 aChauhan, Virander, Singh  uhttps://library.ncl.res.in/content/mechanism-action-novel-synthetic-dodecapeptides-against-candida-albicans-001584nas a2200169   4500008004100000245007000041210006900111260000800180300001400188490000800202520101100210100001701221700002501238700002401263700002601287856010101313       2016                        eng d00aFungal cell membrane-promising drug target for antifungal therapy0 aFungal cell membranepromising drug target for antifungal therapy  cDEC  a1498-15100 v1213 aIncrease in invasive fungal infections over the past few years especially in immunocompromised patients prompted the search for new antifungal agents with improved efficacy. Current antifungal armoury includes very few effective drugs like Amphotericin B; new generation azoles, including voriconazole and posaconazole; echinocandins like caspofungin and micafungin to name a few. Azole class of antifungals which target the fungal cell membrane are the first choice of treatment for many years because of their effectiveness. As the fungal cell membrane is predominantly made up of sterols, glycerophospholipids and sphingolipids, the role of lipids in pathogenesis and target identification for improved therapeutics were largely pursued by researchers during the last few years. Present review focuses on cell membrane as an antifungal target with emphasis on membrane biogenesis, structure and function of cell membrane, cell membrane inhibitors, screening assays, recent advances and future prospects.1 aSant, D., G.1 aTupe, Santosh, Genba1 aRamana, Chepuri, V.1 aDeshpande, Mukund, V.  uhttps://library.ncl.res.in/content/fungal-cell-membrane-promising-drug-target-antifungal-therapy