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antifungal agents

Ross D Blundell, Simon J Williams, Samantha D M Arras, Jessica L Chitty, Kirsten L Blake, Daniel J Ericsson, Nidhi Tibrewal, Jurgen Rohr, Y Q Andre E Koh, Ulrike Kappler, Avril A B Robertson, Mark S Butler, Matthew A Cooper, Bostjan Kobe, James A Fraser
Opportunistic fungal pathogens such as Cryptococcus neoformans are a growing cause of morbidity and mortality among immunocompromised populations worldwide. To address the current paucity of antifungal therapeutic agents, further research into fungal-specific drug targets is required. Adenylosuccinate synthetase (AdSS) is a crucial enzyme in the adeosine triphosphate (ATP) biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. We have investigated the potential of this enzyme as an antifungal drug target, finding that loss of function results in adenine auxotrophy in C...
September 9, 2016: ACS Infectious Diseases
Petra Füredi, Zsófia Edit Pápay, Kristóf Kovács, Borbála Dalmadi Kiss, Krisztina Ludányi, István Antal, Imre Klebovich
The number of topical fungal infections is growing, mostly owing to immunosuppressive therapy. Several topical fungal infections, such as eye mycoses, can be treated by local administration of antimycotic drugs. One major group of the antifungal agents is triazole, such as voriconazole (VCZ), which is used as the first line treatment of aspergillosis. A disadvantage of VCZ is its low water solubility making the drug difficult to administer in a liquid preparation. The lipid-based nanoparticles (LNP) have attracted increasing attention due to their advantageous properties...
October 1, 2016: Journal of Pharmaceutical and Biomedical Analysis
Nicole Robbins, Michaela Spitzer, Wenliang Wang, Nicholas Waglechner, Dhruv J Patel, Jonathan S O'Brien, Linda Ejim, Obi Ejim, Mike Tyers, Gerard D Wright
Natural products are invaluable historic sources of drugs for infectious diseases; however, the discovery of novel antimicrobial chemical scaffolds has waned in recent years. Concurrently, there is a pressing need for improved therapeutics to treat fungal infections. We employed a co-culture screen to identify ibomycin, a large polyketide macrolactone that has preferential killing activity against Cryptococcus neoformans. Using chemical and genome methods, we determined the structure of ibomycin and identified the biosynthetic cluster responsible for its synthesis...
October 7, 2016: Cell Chemical Biology
Edyta Łukowska-Chojnacka, Jolanta Mierzejewska, Małgorzata Milner-Krawczyk, Małgorzata Bondaryk, Monika Staniszewska
With the appearance of the antifungal resistance, novel antifungal agents need to be identified. In this context new 2,5-disubstituted tetrazole derivatives containing benzothiazole, benzoxazole or phenylsulfonyl moiety were synthesized by N-alkylation of aryltetrazole with 2-[(3-chloropropyl)sulfanyl]-1,3-benzothiazole or 2-[(3-chloropropyl)sulfanyl]-1,3-benzoxazole and Michael-type addition of aryltetrazole to phenyl vinyl sulfone. The chemical structures of the synthesized compounds were confirmed by means of (1)H NMR, (13)C NMR, IR and HRMS spectral data...
September 28, 2016: Bioorganic & Medicinal Chemistry
Atefeh Abdollahi Gohar, Hamid Badali, Tahereh Shokohi, Mojtaba Nabili, Nasrin Amirrajab, Maryam Moazeni
Clinical management of fungal diseases is compromised by the emergence of antifungal drug resistance in fungi, which leads to elimination of available drug classes as treatment options. An understanding of antifungal resistance at molecular level is, therefore, essential for the development of strategies to combat the resistance. This study presents the assessment of molecular mechanisms associated with fluconazole resistance in clinical Candida glabrata isolates originated from Iran. Taking seven distinct fluconazole-resistant C...
October 15, 2016: Mycopathologia
Yosra Ben-Fadhel, Sabrina Saltaji, Mohamed Ali Khlifi, Stephane Salmieri, Khanh Dang Vu, Monique Lacroix
The antimicrobial activity of essential oils (EOs), organic acid (OA) salts and natamycin, a natural antifungal produced during fermentation by the bacterium Streptomyces natalensis, was assessed against four pathogens (Escherichia coli O157:H7, Listeria monocytogenes, Salmonella Typhimurium and Aspergillus niger). The Minimum Inhibitory Concentration (MIC) of each antimicrobial (AM) was assessed to determine their efficiency on tested microbial species in order to select the most efficient. Then, the interactions between different antimicrobial compounds showing the lowest MIC were determined by the checkerboard method...
October 11, 2016: International Journal of Food Microbiology
Juliana Hotta, Wilson Gustavo Cral, Vinicius Tatsuyuji Sakima, Vanessa Soares Lara, Vanessa Migliorini Urban, Karin Hermana Neppelenbroek
BACKGROUND: Antifungal agents incorporated into temporary denture resilient liners as drug carries and delivery have been suggested as an alternative treatment for denture stomatitis. However, to test the in vivo biocompatibility of this protocol, standardization of an intraoral device for optimal drug delivery is required. OBJECTIVE: Standardized criteria were produced to adjust an acrylic intraoral device (IOD) for rats feasible for denture stomatitis treatment by sustained drug-delivery based on minimal inhibitory drug concentrations (MICs) of antifungals for Candida albicans biofilm...
October 13, 2016: Current Drug Delivery
Yaseen A M M Elshaier, Assem Barakat, Bander M Al-Qahtany, Abdullah Mohammed Al-Majid, Mohamed H Al-Agamy
A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt₂. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C...
October 9, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
In-Ho Kim, Jae-Ki Choi, Dong-Gun Lee, In Seok Lee, Tae Ho Hong, Young Kyoung You, Ho Jong Chun, Myung Ah Lee
BACKGROUND: The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical significance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). METHODS: Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma...
October 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Eric F Kong, Christina Tsui, Sona Kucharíková, David Andes, Patrick Van Dijck, Mary Ann Jabra-Rizk
: Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat. Candida albicans and Staphylococcus aureus specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied...
October 11, 2016: MBio
Diego Quiroga, Lili Dahiana Becerra, John Sadat-Bernal, Nathalia Vargas, Ericsson Coy-Barrera
An efficient methodology to obtain novel antifungal analogs of brassinin 1 is described. Starting from l-tryptophan 2, N,N'-dialkylthiourea 4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one 5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino}propanoate 6 type compounds were obtained as main products in different ratios depending on the reaction conditions via a tandem dithiocarbamate formation and Michael addition reaction. In order to understand the dependence of the reaction conditions on the mechanism pathway, a DFT/B3LYP study was performed...
October 11, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xiang Yu, Zhiping Che, Hui Xu
Podophyllotoxin and its related aryltetralin cyclolignans belong to a family of significant products that exhibit various biological properties (e.g., cytotoxic, insecticidal, antifungal, antiviral, anti-inflammatory, neurotoxic, immunosuppressive, antirheumatic, antioxidative, antispasmogenic, and hypolipidemic activities). This review provides a survey of podophyllotoxin and its analogs isolated from plants. In particular, recent developments in the elegant total chemical synthesis, structural modifications, biosynthesis, and biotransformation of podophyllotoxin and its analogs are summarized...
October 10, 2016: Chemistry: a European Journal
Hunny Sharma, G Y Yunus, Rohit Agrawal, Monika Kalra, Swati Verma, Supriya Bhattar
INTRODUCTION: From ancient times, plants with medicinal values are being tested and used in the treatment of various infectious diseases. AIMS AND OBJECTIVES: The present in vitro study was designed to assess the antifungal activity of three commonly available medicinal plants Glycyrrhiza glabra, Ficus religiosa, and Plantago major on inhibiting oral Candida albicans in comparison to standard antifungal agents. MATERIALS AND METHODS: Bark of G...
July 2016: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
Jing Shao, GaoXiang Shi, TianMing Wang, DaQiang Wu, ChangZhong Wang
Candida tropicalis has emerged as an important pathogenic fungus in nosocomial infections due to its recalcitrant resistance to conventional antifungal agents, especially to fluconazole (FLC). Berberine (BBR) is a bioactive herbal-originated alkaloids and has been reported to possess antifungal functions against C. albicans. In this paper, we tried to figure out the antifungal mechanisms of BBR and/or FLC in a clinical C. tropicalis isolate 2006. In the microdilution test, the minimum inhibitory concentration (MIC) of BBR was found 16 μg/mL with fractional inhibitory concentration index (FICI) 0...
2016: Frontiers in Microbiology
Marc Pihet, Yohann Le Govic
Dermatophytoses include a wide variety of diseases involving glabrous skin, nails and hair. These superficial infections are a common cause of consultation in dermatology. In many cases, their diagnosis is not clinically obvious, and mycological analysis therefore is required. Direct microscopic examination of the samples using clearing agents provides a quick response to the clinician and is usually combined with cultures on specific media, which must be used to overcome the growth of contaminating moulds that may hamper the recovery of dermatophytes...
October 7, 2016: Mycopathologia
Qian Zhang, Madher N Alfindee, Jaya P Shrestha, Vincent de Paul Nzuwah Nziko, Yukie Kawasaki, Xinrui Peng, Jon Y Takemoto, Cheng-Wei Tom Chang
A concise and novel method for site-selective alkylation of 1,3,6',3″-tetraazidokanamycin has been developed that leads to the divergent synthesis of three classes of kanamycin A derivatives. These new amphiphilic kanamycin derivatives bearing alkyl chains length of 4, 6, 7, 8, 9, 10, 12, 14 and 16 have been tested for their antibacterial and antifungal activities. The antibacterial effect of the synthesized kanamycin derivatives decline or disappear compared to the original kanamycin A, Several compounds, especially those with octyl chain at O-4″ and/or O-6″ positions on the ring III of kanamycin A show very strong activity as antifungal agents...
October 7, 2016: Journal of Organic Chemistry
Maria Clara Padovani de Souza, Andrezza Gouvêa Dos Santos, Adriano Max Moreira Reis
Background The inappropriate use of systemic antifungal agents can result in unnecessary exposure, adverse events, increased microbial resistance and increased costs. Aim This study analysed the use of systemic antifungal agents and adherence to treatment guidelines for fungal infections. Setting A Brazilian tertiary hospital. Methods This cross-sectional study investigated 183 patients who were treated with systemic antifungals. Antifungal drugs were classified according to the fourth level of the Anatomical Therapeutic Chemical classification system...
October 6, 2016: International Journal of Clinical Pharmacy
Shankar Thangamani, Hassan E Eldesouky, Haroon Mohammad, Pete E Pascuzzi, Larisa Avramova, Tony R Hazbun, Mohamed N Seleem
BACKGROUND: Ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear. METHODS: The antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, Cryptococcus neoformans, and C. gattii clinical isolates. Chemogenomic profiling and biochemical assays were employed to identify the antifungal target of ebselen...
October 3, 2016: Biochimica et Biophysica Acta
Margaret L Barlow, Ryan J Cummings, Alice P Pentland, Tanzy M T Love, Constantine G Haidaris, Julie L Ryan, Edith M Lord, Scott A Gerber
Exposure to radiation, particularly a large or total-body dose, weakens the immune system through loss of bone marrow precursor cells, as well as diminished populations of circulating and tissue-resident immune cells. One such population is the skin-resident immune cells. Changes in the skin environment can be of particular importance as the skin is also host to a number of commensal organisms, including Candida albicans , a species of fungus that causes opportunistic infections in immunocompromised patients...
October 6, 2016: Radiation Research
Marta Maciejewska, Delphine Adam, Loïc Martinet, Aymeric Naômé, Magdalena Całusińska, Philippe Delfosse, Monique Carnol, Hazel A Barton, Marie-Pierre Hayette, Nicolas Smargiasso, Edwin De Pauw, Marc Hanikenne, Denis Baurain, Sébastien Rigali
Moonmilk speleothems of limestone caves host a rich microbiome, among which Actinobacteria represent one of the most abundant phyla. Ancient medical texts reported that moonmilk had therapeutical properties, thereby suggesting that its filamentous endemic actinobacterial population might be a source of natural products useful in human treatment. In this work, a screening approach was undertaken in order to isolate cultivable Actinobacteria from moonmilk of the Grotte des Collemboles in Belgium, to evaluate their taxonomic profile, and to assess their potential in biosynthesis of antimicrobials...
2016: Frontiers in Microbiology
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