Highly Potent 1H-1,2,3-Triazole-Tethered Isatin-Metronidazole Conjugates Against Anaerobic Foodborne, Waterborne, and Sexually-Transmitted Protozoal Parasites.

Abstract:

:Parasitic infections like amebiasis, trichomoniasis, and giardiasis are major health threats in tropical and subtropical regions of the world. Metronidazole (MTZ) is the current drug of choice for amebiasis, giardiasis, and trichomoniasis but it has several adverse effects and potential resistance is a concern. In order to develop alternative antimicrobials, a library of 1H-1,2,3-triazole-tethered metronidazole-isatin conjugates was synthesized using Huisgen's azide-alkyne cycloaddition reaction and evaluated for their amebicidal, anti-trichomonal, and anti-giardial potential. Most of the synthesized conjugates exhibited activities against Trichomonas vaginalis, Tritrichomonas foetus, Entamoeba histolytica, and Giardia lamblia. While activities against T. vaginalis and T. foetus were comparable to that of the standard drug MTZ, better activities were observed against E. histolytica and G. lamblia. Conjugates 9d and 10a were found to be 2-3-folds more potent than MTZ against E. histolytica and 8-16-folds more potent than MTZ against G. lamblia. Further analysis of these compounds on fungi and bacteria did not show inhibitory activity, demonstrating their specific anti-protozoal properties.

authors

Kumar S,Bains T,Won Kim AS,Tam C,Kim J,Cheng LW,Land KM,Debnath A,Kumar V

doi

10.3389/fcimb.2018.00380

subject

Has Abstract

pub_date

2018-10-30 00:00:00

pages

380

issn

2235-2988

journal_volume

8

pub_type

杂志文章
  • Genetic Diversity and Phylogeography of Thottapalayam thottimvirus (Hantaviridae) in Asian House Shrew (Suncus murinus) in Eurasia.

    abstract::Murid and cricetid rodents were previously believed to be the principal reservoir hosts of hantaviruses. Recently, however, multiple newfound hantaviruses have been discovered in shrews, moles, and bats, suggesting a complex evolutionary history. Little is known about the genetic diversity and geographic distribution ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2020.00438

    authors: Kikuchi F,Aoki K,Ohdachi SD,Tsuchiya K,Motokawa M,Jogahara T,Sơn NT,Bawm S,Lin KS,Thwe TL,Gamage CD,Ranorosoa MC,Omar H,Maryanto I,Suzuki H,Tanaka-Taya K,Morikawa S,Mizutani T,Suzuki M,Yanagihara R,Arai S

    更新日期:2020-08-27 00:00:00

  • Population Genomics of Francisella tularensis subsp. holarctica and its Implication on the Eco-Epidemiology of Tularemia in Switzerland.

    abstract::Whole genome sequencing (WGS) methods provide new possibilities in the field of molecular epidemiology. This is particularly true for monomorphic organisms where the discriminatory power of traditional methods (e.g., restriction enzyme length polymorphism typing, multi locus sequence typing etc.) is inadequate to eluc...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2018.00089

    authors: Wittwer M,Altpeter E,Pilo P,Gygli SM,Beuret C,Foucault F,Ackermann-Gäumann R,Karrer U,Jacob D,Grunow R,Schürch N

    更新日期:2018-03-22 00:00:00

  • Curcumin Blocks Cytotoxicity of Enteroaggregative and Enteropathogenic Escherichia coli by Blocking Pet and EspC Proteolytic Release From Bacterial Outer Membrane.

    abstract::Pet and EspC are toxins secreted by enteroaggregative (EAEC) and enteropathogenic (EPEC) diarrheagenic Escherichia coli pathotypes, respectively. Both toxins are members of the Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) family. Pet and EspC are important virulence factors that produce cytotoxic an...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2019.00334

    authors: Sanchez-Villamil JI,Navarro-Garcia F,Castillo-Romero A,Gutierrez-Gutierrez F,Tapia D,Tapia-Pastrana G

    更新日期:2019-09-25 00:00:00

  • Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism.

    abstract::Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNγ, CD4+, and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2016.00004

    authors: Bernal CE,Zorro MM,Sierra J,Gilchrist K,Botero JH,Baena A,Ramirez-Pineda JR

    更新日期:2016-02-02 00:00:00

  • Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

    abstract::HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive.H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. p...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2017.00376

    authors: Lucero Y,Oyarzún A,O'Ryan M,Quera R,Espinosa N,Valenzuela R,Simian D,Alcalde E,Arce C,Farfán MJ,Vergara AF,Gajardo I,Mendez J,Carrasco J,Errázuriz G,Gonzalez M,Ossa JC,Maiza E,Perez-Bravo F,Castro M,Araya M

    更新日期:2017-08-23 00:00:00

  • The Entamoeba histolytica Syf1 Homolog Is Involved in the Splicing of AG-Dependent and AG-Independent Transcripts.

    abstract::Syf1 is a tetratricopeptide repeat (TPR) protein implicated in transcription elongation, spliceosome conformation, mRNA nuclear-cytoplasmic export and transcription-coupled DNA repair. Recently, we identified the spliceosomal components of the human parasite Entamoeba histolytica, among them is EhSyf. Molecular predic...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2018.00229

    authors: Torres-Cifuentes DM,Galindo-Rosales JM,Saucedo-Cárdenas O,Valdés J

    更新日期:2018-07-09 00:00:00

  • TLR2-/- Mice Display Increased Clearance of Dermatophyte Trichophyton mentagrophytes in the Setting of Hyperglycemia.

    abstract::Dermatophytosis is one of the most common human infections affecting both immunocompetent individuals and immunocompromised patients, in whom the disease is more aggressive and can reach deep tissues. Over the last decades, cases of deep dermatophytosis have increased and the dermatophyte-host interplay remains poorly...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2017.00008

    authors: Almeida DF,Fraga-Silva TF,Santos AR,Finato AC,Marchetti CM,Golim MA,Lara VS,Arruda MS,Venturini J

    更新日期:2017-01-20 00:00:00

  • Molecular Characterization of a Prevalent Ribocluster of Methicillin-Sensitive Staphylococcus aureus from Orthopedic Implant Infections. Correspondence with MLST CC30.

    abstract::Staphylococcus aureus is the leading etiologic agent of orthopedic implant infections. Here a ribocluster of 27 S. aureus strains underwent further molecular characterization and subtyping by multilocus sequence typing (MLST) and spa-typing. This cluster had been detected by automated ribotyping (with the EcoRI restri...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2016.00008

    authors: Montanaro L,Ravaioli S,Ruppitsch W,Campoccia D,Pietrocola G,Visai L,Speziale P,Allerberger F,Arciola CR

    更新日期:2016-02-16 00:00:00

  • Entamoeba histolytica EhCP112 Dislocates and Degrades Claudin-1 and Claudin-2 at Tight Junctions of the Intestinal Epithelium.

    abstract::During intestinal invasion, Entamoeba histolytica opens tight junctions (TJs) reflected by transepithelial electrical resistance (TEER) dropping. To explore the molecular mechanisms underlying this, we studied in vitro and in vivo the damage produced by the recombinant E. histolytica cysteine protease (rEhCP112) on TJ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2017.00372

    authors: Cuellar P,Hernández-Nava E,García-Rivera G,Chávez-Munguía B,Schnoor M,Betanzos A,Orozco E

    更新日期:2017-08-16 00:00:00

  • Burkholderia pseudomallei BimC Is Required for Actin-Based Motility, Intracellular Survival, and Virulence.

    abstract::The intracellular pathogen Burkholderia pseudomallei, the etiological agent of melioidosis in humans and various animals, is capable of survival and movement within the cytoplasm of host cells by a process known as actin-based motility. The bacterial factor BimA is required for actin-based motility through its direct ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2019.00063

    authors: Srinon V,Chaiwattanarungruengpaisan S,Korbsrisate S,Stevens JM

    更新日期:2019-03-22 00:00:00

  • Stenotrophomonas maltophilia responds to exogenous AHL signals through the LuxR solo SmoR (Smlt1839).

    abstract::Quorum Sensing (QS) mediated by Acyl Homoserine Lactone (AHL) molecules are probably the most widespread and studied among Gram-negative bacteria. Canonical AHL systems are composed by a synthase (LuxI family) and a regulator element (LuxR family), whose genes are usually adjacent in the genome. However, incomplete AH...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2015.00041

    authors: Martínez P,Huedo P,Martinez-Servat S,Planell R,Ferrer-Navarro M,Daura X,Yero D,Gibert I

    更新日期:2015-05-15 00:00:00

  • Activation of Host IRE1α-Dependent Signaling Axis Contributes the Intracellular Parasitism of Brucella melitensis.

    abstract::Brucella spp. are intracellular vacuolar pathogens that causes brucellosis, a worldwide zoonosis of profound importance. We previously demonstrated that the activity of host unfolded protein response (UPR) sensor IRE1α (inositol-requiring enzyme 1) and ER-associated autophagy confer susceptibility to Brucella melitens...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2018.00103

    authors: Pandey A,Lin F,Cabello AL,da Costa LF,Feng X,Feng HQ,Zhang MZ,Iwawaki T,Rice-Ficht A,Ficht TA,de Figueiredo P,Qin QM

    更新日期:2018-04-20 00:00:00

  • Identification of the PANoptosome: A Molecular Platform Triggering Pyroptosis, Apoptosis, and Necroptosis (PANoptosis).

    abstract::Programmed cell death plays crucial roles in organismal development and host defense. Recent studies have highlighted mechanistic overlaps and extensive, multifaceted crosstalk between pyroptosis, apoptosis, and necroptosis, three programmed cell death pathways traditionally considered autonomous. The growing body of ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2020.00237

    authors: Christgen S,Zheng M,Kesavardhana S,Karki R,Malireddi RKS,Banoth B,Place DE,Briard B,Sharma BR,Tuladhar S,Samir P,Burton A,Kanneganti TD

    更新日期:2020-05-29 00:00:00

  • The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis.

    abstract::For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathologi...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2020.586923

    authors: Rahman MA,Glasgow JN,Nadeem S,Reddy VP,Sevalkar RR,Lancaster JR Jr,Steyn AJC

    更新日期:2020-11-10 00:00:00

  • Type Three Secretion System in Attaching and Effacing Pathogens.

    abstract::Enteropathogenic Escherichia coli and enterohemorrhagic E. coli are diarrheagenic bacterial human pathogens that cause severe gastroenteritis. These enteric pathotypes, together with the mouse pathogen Citrobacter rodentium, belong to the family of attaching and effacing pathogens that form a distinctive histological ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2016.00129

    authors: Gaytán MO,Martínez-Santos VI,Soto E,González-Pedrajo B

    更新日期:2016-10-21 00:00:00

  • Role of type I interferons in inflammasome activation, cell death, and disease during microbial infection.

    abstract::Interferons (IFNs) were discovered over a half-century ago as antiviral factors. The role of type I IFNs has been studied in the pathogenesis of both acute and chronic microbial infections. Deregulated type I IFN production results in a damaging cascade of cell death, inflammation, and immunological host responses tha...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2013.00077

    authors: Malireddi RK,Kanneganti TD

    更新日期:2013-11-12 00:00:00

  • Long-Term Impact of Toxoplasma gondii Infection on Human Monocytes.

    abstract::Toxoplasma gondii is a prevalent parasite of mammals and birds including up to 30% of humans world-wide. Primary infection of immunocompetent hosts leads to a robust cell-mediated immune response, which controls but does not clear the infection, thus enabling long-term parasite persistence in brain and muscle tissues....

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2019.00235

    authors: Ehmen HG,Lüder CGK

    更新日期:2019-06-28 00:00:00

  • Drosophila as a Model Organism in Host-Pathogen Interaction Studies.

    abstract::Owing to the genetic similarities and conserved pathways between a fruit fly and mammals, the use of the Drosophila model as a platform to unveil novel mechanisms of infection and disease progression has been justified and widely instigated. Gaining proper insight into host-pathogen interactions and identifying chief ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2020.00214

    authors: Younes S,Al-Sulaiti A,Nasser EAA,Najjar H,Kamareddine L

    更新日期:2020-06-23 00:00:00

  • An objective approach for Burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing.

    abstract::Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2012.00120

    authors: Van Zandt KE,Tuanyok A,Keim PS,Warren RL,Gelhaus HC

    更新日期:2012-09-26 00:00:00

  • Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans.

    abstract::Iron is the most abundant transition metal in the human body and its bioavailability is stringently controlled. In particular, iron is tightly bound to host proteins such as transferrin to maintain homeostasis, to limit potential damage caused by iron toxicity under physiological conditions and to restrict access by p...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2013.00080

    authors: Caza M,Kronstad JW

    更新日期:2013-11-19 00:00:00

  • Characterization of the Esophageal Microbiota and Prediction of the Metabolic Pathways Involved in Esophageal Cancer.

    abstract::Esophageal microbiota plays important roles in esophageal cancer. Esophagectomy, as the most important therapeutic way, contributes to changes of esophageal microbiome. However, there are few studies examining the esophageal microbiome and the metabolic changes before and after esophagectomy. The present study charact...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2020.00268

    authors: Li D,He R,Hou G,Ming W,Fan T,Chen L,Zhang L,Jiang W,Wang W,Lu Z,Feng H,Geng Q

    更新日期:2020-06-26 00:00:00

  • BtpB, a novel Brucella TIR-containing effector protein with immune modulatory functions.

    abstract::Several bacterial pathogens have TIR domain-containing proteins that contribute to their pathogenesis. We identified a second TIR-containing protein in Brucella spp. that we have designated BtpB. We show it is a potent inhibitor of TLR signaling, probably via MyD88. BtpB is a novel Brucella effector that is translocat...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2013.00028

    authors: Salcedo SP,Marchesini MI,Degos C,Terwagne M,Von Bargen K,Lepidi H,Herrmann CK,Santos Lacerda TL,Imbert PR,Pierre P,Alexopoulou L,Letesson JJ,Comerci DJ,Gorvel JP

    更新日期:2013-07-08 00:00:00

  • Toll-like receptors are critical for clearance of Brucella and play different roles in development of adaptive immunity following aerosol challenge in mice.

    abstract::Brucella spp. cause undulant fever in humans and brucellosis in variety of other animals. Both innate and adaptive immunity have been shown to be important in controlling Brucella infection. Toll-like receptors (TLRs) represent a group of pattern recognition receptors (PRRs) that play critical roles in the host innate...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2012.00115

    authors: Pei J,Ding X,Fan Y,Rice-Ficht A,Ficht TA

    更新日期:2012-09-07 00:00:00

  • Bacteriophages: an underestimated role in human and animal health?

    abstract::Metagenomic approaches applied to viruses have highlighted their prevalence in almost all microbial ecosystems investigated. In all ecosystems, notably those associated with humans or animals, the viral fraction is dominated by bacteriophages. Whether they contribute to dysbiosis, i.e., the departure from microbiota c...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2014.00039

    authors: De Paepe M,Leclerc M,Tinsley CR,Petit MA

    更新日期:2014-03-28 00:00:00

  • Alterations to the Lung Microbiome in Idiopathic Pulmonary Fibrosis Patients.

    abstract::Lung microbiome ecosystem homeostasis in idiopathic pulmonary fibrosis (IPF) remains uncharacterized. The aims of this study were to identify unique microbial signatures of the lung microbiome and analyze microbial gene function in IPF patients. DNA isolated from BALF samples was obtained for high-throughput gene sequ...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2019.00149

    authors: Tong X,Su F,Xu X,Xu H,Yang T,Xu Q,Dai H,Huang K,Zou L,Zhang W,Pei S,Xiao F,Li Y,Wang C

    更新日期:2019-05-21 00:00:00

  • Pyrosequencing 16S rRNA genes of bacteria associated with wild tiger mosquito Aedes albopictus: a pilot study.

    abstract::The Asian tiger mosquito Aedes (Stegomya) albopictus is an invasive species that has spread across the world in the last two decades, showing a great capacity to adapt to contrasting climates and environments. While demonstrated in many insects, the contribution of bacterial symbionts in Aedes ecology is a challenging...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2014.00059

    authors: Minard G,Tran FH,Dubost A,Tran-Van V,Mavingui P,Moro CV

    更新日期:2014-05-14 00:00:00

  • The Transcriptome of Exophiala dermatitidis during Ex-vivo Skin Model Infection.

    abstract::The black yeast Exophiala dermatitidis is a widespread polyextremophile and human pathogen, that is found in extreme natural habitats and man-made environments such as dishwashers. It can cause various diseases ranging from phaeohyphomycosis and systemic infections, with fatality rates reaching 40%. While the number o...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2016.00136

    authors: Poyntner C,Blasi B,Arcalis E,Mirastschijski U,Sterflinger K,Tafer H

    更新日期:2016-10-24 00:00:00

  • A comparison of the endotoxin biosynthesis and protein oxidation pathways in the biogenesis of the outer membrane of Escherichia coli and Neisseria meningitidis.

    abstract::The Gram-negative bacterial cell envelope consists of an inner membrane (IM) that surrounds the cytoplasm and an asymmetrical outer-membrane (OM) that forms a protective barrier to the external environment. The OM consists of lipopolysaccahride (LPS), phospholipids, outer membrane proteins (OMPs), and lipoproteins. Ox...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章,评审

    doi:10.3389/fcimb.2012.00162

    authors: Piek S,Kahler CM

    更新日期:2012-12-20 00:00:00

  • Microbial Pre-exposure and Vectorial Competence of Anopheles Mosquitoes.

    abstract::Anopheles female mosquitoes can transmit Plasmodium, the malaria parasite. During their aquatic life, wild Anopheles mosquito larvae are exposed to a huge diversity of microbes present in their breeding sites. Later, adult females often take successive blood meals that might also carry different micro-organisms, inclu...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2017.00508

    authors: Dieme C,Rotureau B,Mitri C

    更新日期:2017-12-07 00:00:00

  • Francisella novicida Two-Component System Response Regulator BfpR Modulates iglC Gene Expression, Antimicrobial Peptide Resistance, and Biofilm Production.

    abstract::Response regulators are a critical part of the two-component system of gene expression regulation in bacteria, transferring a signal from a sensor kinase into DNA binding activity resulting in alteration of gene expression. In this study, we investigated a previously uncharacterized response regulator in Francisella n...

    journal_title:Frontiers in cellular and infection microbiology

    pub_type: 杂志文章

    doi:10.3389/fcimb.2020.00082

    authors: Dean SN,Milton ME,Cavanagh J,van Hoek ML

    更新日期:2020-03-13 00:00:00