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Souza CMD, Bezerra BT, Mellon DA, de Oliveira HC. The evolution of antifungal therapy: Traditional agents, current challenges and future perspectives. CURRENT RESEARCH IN MICROBIAL SCIENCES 2025; 8:100341. [PMID: 39897698 PMCID: PMC11786858 DOI: 10.1016/j.crmicr.2025.100341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2025] Open
Abstract
Fungal infections kill more than 3 million people every year. This high number reflects the significant challenges that treating these diseases worldwide presents. The current arsenal of antifungal drugs is limited and often accompanied by high toxicity to patients, elevated treatment costs, increased frequency of resistance rates, and the emergence of naturally resistant species. These treatment challenges highlight the urgency of developing new antifungal therapies, which could positively impact millions of lives each year globally. Our review offers an overview of the antifungal drugs currently available for treatment, presents the status of new antifungal drugs under clinical study, and explores ahead to future candidates that aim to help address this important global health issue.
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Affiliation(s)
| | | | - Daniel Agreda Mellon
- Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, PR, Brazil
- Programa de Pós-Graduação em Biologia Parasitária, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil
| | - Haroldo Cesar de Oliveira
- Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, PR, Brazil
- Department of Microbiology, Immunology, and Parasitology, Discipline of Cellular Biology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
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In silico and multi-spectroscopic analyses on the interaction of 5-amino-8-hydroxyquinoline and bovine serum albumin as a potential anticancer agent. Sci Rep 2021; 11:20187. [PMID: 34642420 PMCID: PMC8511024 DOI: 10.1038/s41598-021-99690-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 09/28/2021] [Indexed: 12/20/2022] Open
Abstract
5-Amino-8-hydroxyquinoline (5A8HQ), an amino derivative of 8-hydroxyquinoline, has become a potential anticancer candidate because of its promising proteasome inhibitory activity to overcome and yet synergize bortezomib for fighting cancers. Therefore, in this study, its physicochemical properties and interaction activities with serum protein have extensively been elucidated by both in vitro and in silico approaches to fulfill the pharmacokinetic and pharmacodynamic gaps. 5A8HQ exhibited the drug-likeness properties, where oral administration seems to be a route of choice owing to its high-water solubility and intestinal absorptivity. Multi-spectroscopic investigations suggested that 5A8HQ tended to associate with bovine serum albumin (BSA), a representative of serum protein, via the ground-state complexation. It apparently bound in a protein cleft between subdomains IIA and IIIA of BSA as suggested by the molecular docking and molecular dynamics simulations. The binding was mainly driven by hydrogen bonding and electrostatic interactions with a moderate binding constant at 104 M−1, conforming with the predicted free fraction in serum at 0.484. Therefore, 5A8HQ seems to display a good bioavailability in plasma to reach target sites and exerts its potent pharmacological activity. Likewise, serum albumin is a good candidate to be reservoir and transporter of 5A8HQ in the circulatory system.
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dos Reis TF, Horta MAC, Colabardini AC, Fernandes CM, Silva LP, Bastos RW, Fonseca MVDL, Wang F, Martins C, Rodrigues ML, Silva Pereira C, Del Poeta M, Wong KH, Goldman GH. Screening of Chemical Libraries for New Antifungal Drugs against Aspergillus fumigatus Reveals Sphingolipids Are Involved in the Mechanism of Action of Miltefosine. mBio 2021; 12:e0145821. [PMID: 34372704 PMCID: PMC8406317 DOI: 10.1128/mbio.01458-21] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 07/06/2021] [Indexed: 12/16/2022] Open
Abstract
Aspergillus fumigatus is an important fungal pathogen and the main etiological agent of aspergillosis, a disease characterized by a noninvasive process that can evolve to a more severe clinical manifestation, called invasive pulmonary aspergillosis (IPA), in immunocompromised patients. The antifungal arsenal to threat aspergillosis is very restricted. Azoles are the main therapeutic approach to control IPA, but the emergence of azole-resistant A. fumigatus isolates has significantly increased over recent decades. Therefore, new strategies are necessary to combat aspergillosis, and drug repurposing has emerged as an efficient and alternative approach for identifying new antifungal drugs. Here, we used a screening approach to analyze A. fumigatus in vitro susceptibility to 1,127 compounds. A. fumigatus was susceptible to 10 compounds, including miltefosine, a drug that displayed fungicidal activity against A. fumigatus. By screening an A. fumigatus transcription factor null library, we identified a single mutant, which has the smiA (sensitive to miltefosine) gene deleted, conferring a phenotype of susceptibility to miltefosine. The transcriptional profiling (RNA-seq) of the wild-type and ΔsmiA strains and chromatin immunoprecipitation coupled to next-generation sequencing (ChIP-Seq) of an SmiA-tagged strain exposed to miltefosine revealed genes of the sphingolipid pathway that are directly or indirectly regulated by SmiA. Sphingolipid analysis demonstrated that the mutant has overall decreased levels of sphingolipids when growing in the presence of miltefosine. The identification of SmiA represents the first genetic element described and characterized that plays a direct role in miltefosine response in fungi. IMPORTANCE The filamentous fungus Aspergillus fumigatus causes a group of diseases named aspergillosis, and their development occurs after the inhalation of conidia dispersed in the environment. Very few classes of antifungal drugs are available for aspergillosis treatment, e.g., azoles, but the emergence of global resistance to azoles in A. fumigatus clinical isolates has increased over recent decades. Repositioning or repurposing drugs already available on the market is an interesting and faster opportunity for the identification of novel antifungal agents. By using a repurposing strategy, we identified 10 different compounds that impact A. fumigatus survival. One of these compounds, miltefosine, demonstrated fungicidal activity against A. fumigatus. The mechanism of action of miltefosine is unknown, and, aiming to get more insights about it, we identified a transcription factor, SmiA (sensitive to miltefosine), important for miltefosine resistance. Our results suggest that miltefosine displays antifungal activity against A. fumigatus, interfering in sphingolipid biosynthesis.
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Affiliation(s)
- Thaila Fernanda dos Reis
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
- MicroControl Innovation Ltd., Ribeirão Preto, São Paulo, Brazil
| | | | - Ana Cristina Colabardini
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
| | - Caroline Mota Fernandes
- Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New York, USA
| | - Lilian Pereira Silva
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
| | - Rafael Wesley Bastos
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
| | | | - Fang Wang
- Faculty of Health Sciences, University of Macau, Taipa, Macau, SAR, China
| | - Celso Martins
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), Oeiras, Portugal
| | - Márcio L. Rodrigues
- Instituto Carlos Chagas (ICC), Fundação Oswaldo Cruz–Fiocruz, Curitiba, Brazil
- Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Cristina Silva Pereira
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), Oeiras, Portugal
| | - Maurizio Del Poeta
- Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New York, USA
- Veteran Administration Medical Center, Northport, New York, USA
- MicroRid Technologies Inc., Dix Hills, New York, USA
- Division of Infectious Diseases, School of Medicine, Stony Brook University, New York, USA
| | - Koon Ho Wong
- Faculty of Health Sciences, University of Macau, Taipa, Macau, SAR, China
- Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, SAR, China
- MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, SAR, China
| | - Gustavo H. Goldman
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
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Borba-Santos LP, Vila T, Rozental S. Identification of two potential inhibitors of Sporothrix brasiliensis and Sporothrix schenckii in the Pathogen Box collection. PLoS One 2020; 15:e0240658. [PMID: 33052959 PMCID: PMC7556523 DOI: 10.1371/journal.pone.0240658] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Sporotrichosis is a neglected endemic mycosis with a high incidence in Latin America, mainly in Brazil. Sporothrix schenckii is the most frequent species in Latin America, whereas Sporothrix brasiliensis is the predominant species observed in Brazil and is associated with both human and animal sporotrichosis. Sporotrichosis treatment remains restricted to a few options, itraconazole being the first choice for human and animal therapy. In this work, we screened the molecular library Pathogen Box (Medicines for Malaria Venture [MMV], Switzerland) in search of compounds with anti-Sporothrix activity. Our initial screen of the 400 compounds identified five compounds that inhibited more than 80% of S. brasiliensis and S. schenkii growth. Among those, three compounds (MMV675968, MMV102872, and MMV002817 (known as iodoquinol)) not previously described as antifungals or agrochemicals, were selected for further evaluation. MMV102872 and iodoquinol showed the most promising combination of antifungal activity (lower inhibitory concentration) and fungal selectivity (lower cytotoxicity in LLC-MK2 cells). Scanning electron microscopy and flow cytometry analyses revealed that MMV102872 and iodoquinol induced changes in cell morphology, membrane integrity, and the presence of neutral lipids, impairing fungal survival. Our results indicate that MMV102872 and iodoquinol are promising molecules for use as scaffolds for the development of new antifungal agents.
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Affiliation(s)
- Luana Pereira Borba-Santos
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
- * E-mail:
| | - Taissa Vila
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Sonia Rozental
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
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Petersen K, Regis DP. Safety of antimalarial medications for use while scuba diving in malaria Endemic Regions. TROPICAL DISEASES TRAVEL MEDICINE AND VACCINES 2017; 2:23. [PMID: 28883967 PMCID: PMC5530948 DOI: 10.1186/s40794-016-0041-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 10/07/2016] [Indexed: 11/24/2022]
Abstract
Background Recreational diving occurs annually in areas of the world where malaria is endemic. The safety and efficacy of antimalarials for travelers in a hyperbaric environment is unknown. Of particular concern would be medications with adverse effects that could either mimic diving related illnesses such as barotrauma, decompression sickness (DCS) and gas toxicities, or increase the risk for such illnesses. Methods We conducted a review of PubMed and Cochrane databases to determine rates of neurologic adverse effects or other effects from antimalarials that may be a problem in the diving environment. Results One case report was found on diving and mefloquine. Multiple case reports and clinical trials were found describing neurologic adverse effects of the major chemoprophylactic medications atovaquone/proguanil, chloroquine, doxycycline, mefloquine, and primaquine. Conclusions Of the available literature, atovaquone/proguanil and doxycycline are most likely the safest agents and should be preferred; atovaquone/proguanil is superior due to reduced rates of sunburn in the marine environment. Primaquine also appears to be safe, but has reduced efficacy against P. falciparum; mefloquine possesses the highest rate of neurologic side effects and therefore these agents should be limited to extreme cases of patients intolerant to other agents. Chloroquine appears unsafe in the hyperbaric environment and should be avoided. More studies are required to include database reviews of returned divers traveling to malaria endemic areas and randomized controlled trials in the hyperbaric environments.
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Affiliation(s)
- Kyle Petersen
- Department of Medicine, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA
| | - David P Regis
- Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA
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Yang T, Wang S, Zhang X, Xia J, Guo J, Hou J, Zhang H, Chen X, Wu X. A Rapid and Convenient Method for in Vivo Fluorescent Imaging of Protoscolices of Echinococcus multilocularis. THE KOREAN JOURNAL OF PARASITOLOGY 2016; 54:225-31. [PMID: 27180584 PMCID: PMC4870970 DOI: 10.3347/kjp.2016.54.2.225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Revised: 02/01/2016] [Accepted: 02/01/2016] [Indexed: 11/23/2022]
Abstract
Human and animal alveolar echinococcosis (AE) are important helminth infections endemic in wide areas of the Northern hemisphere. Monitoring Echinococcus multilocularis viability and spread using real-time fluorescent imaging in vivo provides a fast method to evaluate the load of parasite. Here, we generated a kind of fluorescent protoscolices in vivo imaging model and utilized this model to assess the activity against E. multilocularis protoscolices of metformin (Met). Results indicated that JC-1 tagged E. multilocularis can be reliably and confidently used to monitor protoscolices in vitro and in vivo. The availability of this transient in vivo fluorescent imaging of E. multilocularis protoscolices constitutes an important step toward the long term bio-imaging research of the AE-infected mouse models. In addition, this will be of great interest for further research on infection strategies and development of drugs and vaccines against E. multilocularis and other cestodes.
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Affiliation(s)
- Tao Yang
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Sibo Wang
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Xuyong Zhang
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Jie Xia
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Jun Guo
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Jixue Hou
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Hongwei Zhang
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Xueling Chen
- Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Xiangwei Wu
- Department of General Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.,Laboratory of Transitional Medicine, Shihezi University School of Medicine, Shihezi, Xinjiang, China
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Nagata N, Marriott D, Harkness J, Ellis JT, Stark D. Current treatment options for Dientamoeba fragilis infections. INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE 2012; 2:204-15. [PMID: 24533282 DOI: 10.1016/j.ijpddr.2012.08.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2012] [Revised: 08/06/2012] [Accepted: 08/07/2012] [Indexed: 12/20/2022]
Abstract
Dientamoeba fragilis belongs to the trichomonad group of protozoan parasites and it has been implicated as a cause of gastrointestinal disease with world-wide prevalences ranging from 0.5% to 16%. The majority of patients with dientamoebiasis present with gastrointestinal complaints. Chronic symptoms are common with up to a third of patients exhibiting persistent diarrhoea. Numerous studies have successfully demonstrated parasite clearance, coupled with complete resolution of clinical symptoms following treatment with various antiparasitic compounds. Treatments reported to be successful for dientamoebiasis include carbarsone, diphetarsone, tetracyclines, paromomycin, erythromycin, hydroxyquinolines and the 5-nitroimidazoles, including metronidazole, secnidazole, tinidazole and ornidazole. It is of note that most current treatment data is based only on small number of case reports. No large scale double blind randomised placebo controlled trials testing the efficacy of antimicrobial agents against D. fragilis has been undertaken highlighting the need for further study. In addition there is very little in vitro susceptibility data available for the organism making some current treatment options questionable. The aim of this review is to critically discuss all treatment options currently available for dientamoebiasis.
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Affiliation(s)
- Noriyuki Nagata
- Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, Australia ; University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway, Australia
| | - Deborah Marriott
- Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, Australia ; University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway, Australia
| | - John Harkness
- Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, Australia ; University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway, Australia
| | - John T Ellis
- University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway, Australia ; University of Technology Sydney, iThree Institute, Broadway, Australia
| | - Damien Stark
- Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, Australia ; University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway, Australia
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Design of sterculia gum based double potential antidiarrheal drug delivery system. Colloids Surf B Biointerfaces 2010; 82:325-32. [PMID: 20889316 DOI: 10.1016/j.colsurfb.2010.09.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2009] [Revised: 09/04/2010] [Accepted: 09/05/2010] [Indexed: 11/22/2022]
Abstract
In view of the antidiarrheal properties of sterculia gum and ornidazole, an attempt has been made to synthesize novel hydrogels by functionalization of sterculia gum with poly(vinylpyrrolidone) (PVP) for release of the model antidiarrheal drug ornidazole. These hydrogels were characterized with FTIR, SEM, TGA and swelling behavior. Swelling kinetics of the hydrogels and in vitro release dynamics of ornidazole from the drug loaded hydrogels have been studied to determine the mechanism of swelling and drug release from the drug loaded hydrogels. A Fickian diffusion mechanism has been observed for the release of drug from the hydrogels. These hydrogels may have dual actions for the treatment of diarrhea.
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Stark D, Barratt JLN, van Hal S, Marriott D, Harkness J, Ellis JT. Clinical significance of enteric protozoa in the immunosuppressed human population. Clin Microbiol Rev 2009; 22:634-50. [PMID: 19822892 PMCID: PMC2772358 DOI: 10.1128/cmr.00017-09] [Citation(s) in RCA: 128] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Globally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such as Giardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4(+) cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites.
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Affiliation(s)
- D Stark
- Department of Microbiology, St. Vincent's Hospital, Darlinghurst 2010, NSW, Australia.
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Gil C, Bräse S. Solid-Phase Synthesis of Biologically Active Benzoannelated Nitrogen Heterocycles: An Update. ACTA ACUST UNITED AC 2008; 11:175-97. [DOI: 10.1021/cc800102t] [Citation(s) in RCA: 124] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Carmen Gil
- Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain, and Institut für Organische Chemie, Universität Karlsruhe (TH) and Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
| | - Stefan Bräse
- Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain, and Institut für Organische Chemie, Universität Karlsruhe (TH) and Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
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Emami MH, Saberfiroozi MM, Arj A, Taghavi AR, Bagheri-Lankarani K, Dehbashi N, Fattahi MR, Alizadeh M, Kaviani MJ, Bahri-Najafi R, Geramizadeh B, Esmaeili A. Does delayed gastric emptying shorten the H pylori eradication period? A double blind clinical trial. World J Gastroenterol 2006; 12:6310-6315. [PMID: 17072954 PMCID: PMC4088139 DOI: 10.3748/wjg.v12.i39.6310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2006] [Revised: 01/28/2006] [Accepted: 02/24/2006] [Indexed: 02/07/2023] Open
Abstract
AIM To evaluate the gastric emptying inhibitory effects of sugar and levodopa on H pylori eradication period. METHODS A total of 139 consecutive patients were randomized into 6 groups. The participants with peptic ulcer disease or non-ulcer dyspepsia non-responding to other medications who were also H pylori-positive patients either with positive rapid urease test (RUT) or positive histology were included. All groups were pretreated with omeprazole for 2 d and then treated with quadruple therapy regimen (omeprazole, bismuth, tetracycline and metronidazole); all drugs were given twice daily. Groups 1 and 2 were treated for 3 d, groups 3, 4 and 5 for 7 d, and group 6 for 14 d. Groups 1 to 4 received sugar in the form of 10% sucrose syrup. Levodopa was prescribed for groups 1 and 3. Patients in groups 2 and 4 were given placebo for levodopa and groups 5 and 6 received placebos for both sugar and levodopa. Upper endoscopy and biopsies were carried out before treatment and two months after treatment. Eradication of H pylori was assessed by RUT and histology 8 wk later. RESULTS Thirty patients were excluded. Per-protocol analysis showed successful eradication in 53% in group 1, 56% in group 2, 58% in group 3, 33.3% in group 4, 28% in group 5, and 53% in group 6. Eradication rate, patient compliance and satisfaction were not significantly different between the groups. CONCLUSION It seems that adding sugar or levodopa or both to anti H pylori eradication regimens may lead to shorter duration of treatment.
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Affiliation(s)
- Mohammad Hassan Emami
- Isfahan University of Medical Sciences, Poursina Hakim Research Institute, Mail box: 81465-1798, Isfahan, Iran.
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Dunkel M, Fullbeck M, Neumann S, Preissner R. SuperNatural: a searchable database of available natural compounds. Nucleic Acids Res 2006; 34:D678-83. [PMID: 16381957 PMCID: PMC1347494 DOI: 10.1093/nar/gkj132] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2005] [Revised: 10/24/2005] [Accepted: 10/24/2005] [Indexed: 01/22/2023] Open
Abstract
Although tremendous effort has been put into synthetic libraries, most drugs on the market are still natural compounds or derivatives thereof. There are encyclopaedias of natural compounds, but the availability of these compounds is often unclear and catalogues from numerous suppliers have to be checked. To overcome these problems we have compiled a database of approximately 50,000 natural compounds from different suppliers. To enable efficient identification of the desired compounds, we have implemented substructure searches with typical templates. Starting points for in silico screenings are about 2500 well-known and classified natural compounds from a compendium that we have added. Possible medical applications can be ascertained via automatic searches for similar drugs in a free conformational drug database containing WHO indications. Furthermore, we have computed about three million conformers, which are deployed to account for the flexibilities of the compounds when the 3D superposition algorithm that we have developed is used. The SuperNatural Database is publicly available at http://bioinformatics.charite.de/supernatural. Viewing requires the free Chime-plugin from MDL (Chime) or Java2 Runtime Environment (MView), which is also necessary for using Marvin application for chemical drawing.
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Affiliation(s)
- Mathias Dunkel
- Berlin Center of Genome Based Bioinformatics, 3D Datamining Group, Institute of Biochemistry, Charité-University Medicine Berlin, Monbijoustrasse 2, 10117 Berlin, Germany.
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Pu RT, Rosenthal DL. Incidental giardiasis diagnosed by fine-needle aspiration of a phantom cecal “mass”. Diagn Cytopathol 2005; 33:287-8. [PMID: 16138373 DOI: 10.1002/dc.20351] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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