scholarly journals Antimalarial activities of ( Z )-2-(nitroheteroarylmethylene)-3(2 H )-benzofuranone derivatives: In vitro , in vivo assessment and β-hematin formation inhibition activity

2021 ◽  
Author(s):  
Latifeh Navidpour ◽  
Kelly Chibale ◽  
Somayeh Esmaeili ◽  
Azadeh Ghiaee ◽  
Narges Hadjesfandiari ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Inhibition Activity ◽  
Mice Model ◽  
Kb Cells ◽  
Cytotoxic Effects ◽  
Reference Drug ◽  
Insight Into ◽  
In Vivo Assessment

A series of ( Z )-2-(nitroheteroarylmethylene)-3(2 H )-benzofuranones possessing nitroheteroaryls groups of nitroimidazole, nitrofuran and nitrothiophene moieties was screened for antiplasmodium activity against drug-sensitive (3D7) as well as a chloroquine (CQ) and multi-drug resistant (K1) strains of P. falciparum 5-Nitroimidazole and 4-nitroimidazole analogs were highly selective and active against resistant parasites, while 5-nitrofuran and 5-nitrothiophene derivatives were more potent against the 3D7 strain than the K1 strain. Among the synthetic analogues, ( Z )-6-chloro-2-(1-methyl-5-nitroimidazol-2-ylmethylene)-3(2 H )-benzofuranone ( 5h ) exhibited the highest activity (IC 50 : 0.654 nM) against K1 strain and ( Z )-7-methoxy-2-(5-nitrothiophen-2-ylmethylene)-3(2 H )-benzofuranone ( 10g ) showed the highest activity (IC 50 : 0.28 μM) against the 3D7 strain in comparison with CQ (IC 50 s of 3.13 and 206.3 nM against 3D7 and K1 strains, respectively). The more active compounds with IC 50 s lower than 5 μg/mL (∼20 μM) were further studied for their cytotoxicity responses using KB cells. From these studies, 5-nitroimidazole, 4-nitroimidazole and 5-nitrofuran analogues were shown to be cytotoxic against KB cells, while 5-nitrothiophene analogues were shown to have the least cytotoxic effects. To gain some insight into their potential contributing mechanism of action, three derivatives 10e , 10g and 10h (from nitrothiophene subgroup possessing 6-methoxy, 7-methoxy and 6,7-dimethoxy substituents on their benzofuranone moieties, respectively) showing the least toxicity and highest selectivity indices were assessed for their β-hematin formation inhibition activity. 10g demonstrated the highest inhibition activity (IC 50 : 10.78 μM) in comparison with CQ (IC 50 : 2.63 μM) as the reference drug. Finally, these three analogues ( 10e , 10g and 10h ) were further evaluated for their in vivo activity against P. berghei /albino mice model (Peter’s test). Tested analogues were shown to be active, reducing the percentage of erythrocytes that contained parasites by 53.4, 48.8 and 32.4%, respectively.

Activity profile of two 5-nitroindazole derivatives over the moderately drug-resistant Trypanosoma cruzi Y strain (DTU TcII): in vitro and in vivo studies

Parasitology ◽  
2020 ◽  
Vol 147 (11) ◽  
pp. 1216-1228
Author(s):  
Cristina Fonseca-Berzal ◽  
Cristiane França da Silva ◽  
Denise da Gama Jaen Batista ◽  
Gabriel Melo de Oliveira ◽  
José Cumella ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Positive Impact ◽  
Cardiac Cells ◽  
In Vivo Studies ◽  
Drug Resistant ◽  
Activity Profile ◽  
Reference Drug ◽  
Novel Drugs

AbstractIn previous studies, we have identified several families of 5-nitroindazole derivatives as promising antichagasic prototypes. Among them, 1-(2-aminoethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one, (hydrochloride) and 1-(2-acetoxyethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one (compounds 16 and 24, respectively) have recently shown outstanding activity in vitro over the drug-sensitive Trypanosoma cruzi CL strain (DTU TcVI). Here, we explored the activity of these derivatives against the moderately drug-resistant Y strain (DTU TcII), in vitro and in vivo. The outcomes confirmed their activity over replicative forms, showing IC50 values of 0.49 (16) and 5.75 μm (24) towards epimastigotes, 0.41 (16) and 1.17 μm (24) against intracellular amastigotes. These results, supported by the lack of toxicity on cardiac cells, led to better selectivities than benznidazole (BZ). Otherwise, they were not as active as BZ in vitro against the non-replicative form of the parasite, i.e. bloodstream trypomastigotes. In vivo, acute toxicity assays revealed the absence of toxic events when administered to mice. Moreover, different therapeutic schemes pointed to their capability for decreasing the parasitaemia of T. cruzi Y acute infected mice, reaching up to 60% of reduction at the peak day as monotherapy (16), 79.24 and 91.11% when 16 and 24 were co-administered with BZ. These combined therapies had also a positive impact over the mortality, yielding survivals of 83.33 and 66.67%, respectively, while untreated animals reached a cumulative mortality of 100%. These findings confirm the 5-nitroindazole scaffold as a putative prototype for developing novel drugs potentially applicable to the treatment of Chagas disease and introduce their suitability to act in combination with the reference drug.

scholarly journals In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice

2011 ◽  
Vol 53 (3) ◽  
pp. 129-132 ◽  
Author(s):  
Joshua Muli Mutiso ◽  
John Chege Macharia ◽  
Mustafa Barasa ◽  
Evans Taracha ◽  
Alain J. Bourdichon ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Combined Therapy ◽  
Parasite Burden ◽  
Mice Model ◽  
In Vivo Evaluation ◽  
Reference Drug ◽  
Drug Treatments ◽  
Potential Use

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

scholarly journals Characterization of aMycobacterium aviumsubsp.aviumOperon Associated with Virulence and Drug Detoxification

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Mariana Noelia Viale ◽  
Kun Taek Park ◽  
Belén Imperiale ◽  
Andrea Karina Gioffre ◽  
María Alejandra Colombatti Olivieri ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Efflux Pump ◽  
Mice Model ◽  
Toxic Compounds ◽  
Drug Detoxification ◽  
Insight Into ◽  
Knockout Mutation

ThelprG-p55operon ofMycobacterium tuberculosisandMycobacterium bovisis involved in the transport of toxic compounds. P55 is an efflux pump that provides resistance to several drugs, while LprG is a lipoprotein that modulates the host's immune response against mycobacteria. The knockout mutation of this operon severely reduces the replication of both mycobacterial species during infection in mice and increases susceptibility to toxic compounds. In order to gain insight into the function of LprG in theMycobacterium aviumcomplex, in this study, we assayed the effect of the deletion oflprG gene in the D4ER strain ofMycobacterium aviumsubsp.avium. The replacement oflprG gene with a hygromycin cassette caused a polar effect on the expression ofp55. Also, a twofold decrease in ethidium bromide susceptibility was observed and the resistance to the antibiotics rifampicin, amikacin, linezolid, and rifabutin was impaired in the mutant strain. In addition, the mutation decreased the virulence of the bacteria in macrophagesin vitroand in a mice modelin vivo. These findings clearly indicate that functional LprG and P55 are necessary for the correct transport of toxic compounds and for the survival of MAAin vitroandin vivo.

scholarly journals SpoT-mediated NapA upregulation promotes oxidative stress-induced Helicobacter pylori biofilm formation and confers multidrug resistance

2021 ◽  
Author(s):  
Yican Zhao ◽  
Yuying Cai ◽  
Zhenghong Chen ◽  
Huanjie Li ◽  
Zhengzheng Xu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Multidrug Resistance ◽  
Biofilm Formation ◽  
Drug Resistant ◽  
Low Concentrations ◽  
Target Molecules ◽  
H Pylori ◽  
Insight Into

Recently, there is increased incidence of drug-resistant Helicobacter pylori infection. Biofilm formation confers multidrug resistance to bacteria. Moreover, it has been found that the formation of biofilm on the surface of gastric mucosa is an important reason for the difficulty of eradication of H. pylori. The mechanisms underlying H. pylori biofilm formation in vivo have not been elucidated. Reactive oxygen species (ROS) released by the host immune cells in response to H. pylori infection cannot effectively clear the pathogen. Moreover, the extracellular matrix of the biofilm protects the bacteria against ROS-mediated toxicity. This study hypothesized that ROS can promote H. pylori biofilm formation and treatment with low concentrations of hydrogen peroxide (H2O2) promoted this process in vitro. The comparative transcriptome analysis of planktonic and biofilm-forming cells revealed that the expression of SpoT, a (p)ppGpp (guanosine 3'-diphosphate 5'-triphosphate and guanosine 3',5'-bispyrophosphate) synthetase/hydrolase, is upregulated in H2O2-induced biofilms and that knockout of spoT inhibited H. pylori biofilm formation. Additionally, this study examined the key target molecules involved in SpoT regulation using weighted gene co-expression network analysis. The analysis revealed that neutrophil-activating protein (NapA; HP0243) promoted H2O2-induced biofilm formation and conferred multidrug resistance. Furthermore, vitamin C exhibited anti-H. pylori biofilm activity and downregulated the expression of napA in vitro. These findings provide novel insight into the clearance of H. pylori biofilms.

scholarly journals Plant-Derived Extracellular Vesicles: Current Findings,Challenges, and Future Applications

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 411
Author(s):  
Nader Kameli ◽  
Anya Dragojlovic-Kerkache ◽  
Paul Savelkoul ◽  
Frank R. Stassen
Keyword(s):  
Human Health ◽  
Extracellular Vesicles ◽  
Preliminary Results ◽  
In Vivo Experiments ◽  
Health And Disease ◽  
Conducting Research ◽  
Protocol Standardization ◽  
Insight Into

In recent years, plant-derived extracellular vesicles (PDEVs) have gained the interest of many experts in fields such as microbiology and immunology, and research in this field has exponentially increased. These nano-sized particles have provided researchers with a number of interesting findings, making their application in human health and disease very promising. Both in vitro and in vivo experiments have shown that PDEVs can exhibit a multitude of effects, suggesting that these vesicles may have many potential future applications, including therapeutics and nano-delivery of compounds. While the preliminary results are promising, there are still some challenges to face, such as a lack of protocol standardization, as well as knowledge gaps that need to be filled. This review aims to discuss various aspects of PDEV knowledge, including their preliminary findings, challenges, and future uses, giving insight into the complexity of conducting research in this field.

scholarly journals Silver Nanoparticles and Their Antibacterial Applications

2021 ◽  
Vol 22 (13) ◽  
pp. 7202
Author(s):  
Tamara Bruna ◽  
Francisca Maldonado-Bravo ◽  
Paul Jara ◽  
Nelson Caro
Keyword(s):  
Silver Nanoparticles ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Secondary Effects ◽  
Cytotoxic Effects ◽  
Factors Affecting ◽  
Gram Positive Bacteria ◽  
Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

scholarly journals Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  
Keyword(s):  
In Vitro Assays ◽  
Immunomodulatory Activity ◽  
Probiotic Properties ◽  
Protective Effects ◽  
Mice Model ◽  
In Vivo Models ◽  
Food Borne ◽  
Gastrointestinal Conditions

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

Sign in / Sign up

Export Citation Format

Share Document