scholarly journals Antimicrobial Activity of Extracts of Two Native Fruits of Chile: Arrayan (Luma apiculata) and Peumo (Cryptocarya alba)

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 444
Author(s):  
Jitka Viktorová ◽  
Rohitesh Kumar ◽  
Kateřina Řehořová ◽  
Lan Hoang ◽  
Tomas Ruml ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Inhibitory Concentration ◽  
Dependent Manner ◽  
Drug Resistant ◽  
Planktonic Cells ◽  
Fruit Extract ◽  
Concentration Dependent Manner ◽  
Autoinducer 2 ◽  
Resistant Strains ◽  
Drug Resistant Strains

Arrayan and peumo fruits are commonly used in the traditional medicine of Chile. In this study, the concentration of the extracts halving the bacterial viability and biofilms formation and disruption of the drug-sensitive and drug-resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa was determined. The chemical composition of extracts was analyzed by high-resolution liquid chromatography coupled with mass spectrometry (U-HPLC/MS). The arrayan extract (Inhibitory concentration IC50 0.35 ± 0.01 mg/mL) was more effective than peumo extract (IC50 0.53 ± 0.02 mg/mL) in the inhibition of S. aureus planktonic cells. Similarly, the arrayan extract was more effective in inhibiting the adhesion (S. aureus IC50 0.23 ± 0.02 mg/mL, P. aeruginosa IC50 0.29 ± 0.02 mg/mL) than peumo extracts (S. aureus IC50 0.47 ± 0.03 mg/mL, P. aeruginosa IC50 0.35 ± 0.01 mg/mL). Both extracts inhibited quorum sensing in a concentration-dependent manner, and the most significant was the autoinducer-2 type communication inhibition by arrayan extract. Both extracts also disrupted preformed biofilm of P. aeruginosa (arrayan IC50 0.56 ± 0.04 mg/mL, peumo IC50 0.59 ± 0.04 mg/mL). However, neither arrayan nor peumo extracts disrupted S. aureus mature biofilm. U-HPLC/MS showed that both fruit extracts mainly possessed quercetin compounds; the peumo fruit extract also contained phenolic acids and phenylpropanoids. Our results suggested that both extracts could be used as natural antimicrobials for some skin and nosocomial infections.

scholarly journals Use of the NP-40 Detergent-Mediated Assay in Discovery of Inhibitors of β-Hematin Crystallization

2011 ◽  
Vol 55 (7) ◽  
pp. 3363-3369 ◽  
Author(s):  
Rebecca D. Sandlin ◽  
Melissa D. Carter ◽  
Patricia J. Lee ◽  
Jennifer M. Auschwitz ◽  
Susan E. Leed ◽  
...  
Keyword(s):  
Drug Target ◽  
Inhibitory Concentration ◽  
Protozoan Parasite ◽  
Drug Resistant ◽  
Digestive Vacuole ◽  
Content Type ◽  
Parasite Survival ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Important Drug

ABSTRACTThe protozoan parasite responsible for malaria affects over 500 million people each year. Current antimalarials have experienced decreased efficacy due to the development of drug-resistant strains ofPlasmodiumspp., resulting in a critical need for the discovery of new antimalarials. Hemozoin, a crystalline by-product of heme detoxification that is necessary for parasite survival, serves as an important drug target. The quinoline antimalarials, including amodiaquine and chloroquine, act by inhibiting the formation of hemozoin. The formation of this crystal does not occur spontaneously, and recent evidence suggests crystallization occurs in the presence of neutral lipid particles located in the acidic digestive vacuole of the parasite. To mimic these conditions, the lipophilic detergent NP-40 has previously been shown to successfully mediate the formation of β-hematin, synthetic hemozoin. Here, an NP-40 detergent-based assay was successfully adapted for use as a high-throughput screen to identify inhibitors of β-hematin formation. The resulting assay exhibited a favorableZ′ of 0.82 and maximal drift of less than 4%. The assay was used in a pilot screen of 38,400 diverse compounds at a screening concentration of 19.3 μM, resulting in the identification of 161 previously unreported β-hematin inhibitors. Of these, 48 also exhibited ≥90% inhibition of parasitemia in aPlasmodium falciparumwhole-cell assay at a screening concentration of 23 μM. Eight of these compounds were identified to have nanomolar 50% inhibitory concentration values near that of chloroquine in this assay.

scholarly journals Semi-Synthesis of Marine-Derived Ilamycin F Derivatives and Their Antitubercular Activities

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Li ◽  
Zhiyong Liu ◽  
Mingye Hong ◽  
Changli Sun ◽  
Tianyu Zhang ◽  
...  
Keyword(s):  
Prevention And Control ◽  
Inhibitory Concentration ◽  
Drug Resistant ◽  
Structure Activity ◽  
The World ◽  
Resistant Strains ◽  
New Challenges ◽  
Low Cytotoxicity ◽  
Drug Resistant Strains ◽  
And Control

Tuberculosis (TB) is still a global disease threatening people’s lives. With the emergence of multi-drug-resistant Mycobacterium tuberculosis the prevention and control of tuberculosis faces new challenges, and the burden of tuberculosis treatment is increasing among the world. Ilamycins are novel cyclopeptides with potent anti-TB activities, which have a unique target protein against M. tuberculosis and drug-resistant strains. Herein, ilamycin F, a major secondary metabolite isolated from the marine-derived mutant strain Streptomyces atratus SCSIO ZH16 ΔilaR, is used as a scaffold to semi-synthesize eighteen new ilamycin derivatives (ilamycin NJL1–NJL18, 1–18). Our study reveals that four of ilamycin NJLs (1, 6, 8, and 10) have slightly stronger anti-TB activities against Mtb H37Rv (minimum inhibitory concentration, 1.6–1.7 μM) compared with that of ilamycin F on day 14th, but obviously display more potent activities than ilamycin F on day 3rd, indicating anti-TB activities of these derivatives with fast-onset effect. In addition, cytotoxic assays show most ilamycin NJLs with low cytotoxicity except ilamycin NJL1 (1). These findings will promote the further exploration of structure-activity relationships for ilamycins and the development of anti-TB drugs.

scholarly journals Novel isoniazid derivative as promising antituberculosis agent

2020 ◽  
Vol 15 (10) ◽  
pp. 869-879
Author(s):  
Galyna P Volynets ◽  
Michail A Tukalo ◽  
Volodymyr G Bdzhola ◽  
Nataliia M Derkach ◽  
Mykola I Gumeniuk ◽  
...  
Keyword(s):  
Resistant Strain ◽  
Inhibitory Concentration ◽  
Binding Assay ◽  
Isonicotinic Acid ◽  
Drug Resistant ◽  
Major Focus ◽  
Unbound Fraction ◽  
Protein Binding Assay ◽  
Resistant Strains ◽  
Drug Resistant Strains

Background: A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of Mycobacterium tuberculosis. Results: We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward M. tuberculosis H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (1), is active toward isoniazid-resistant strain with minimum inhibitory concentration value of 0.14 μM. This compound is not cytotoxic toward human liver cells (HepG2; IC50 >100 μM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound 1, which potentially exhibits pharmacologic effects, is 57.9%. Conclusion: Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.

scholarly journals Synthesis of 7, 8 –dihydroxyflavone functionalized gold nanoparticles and its mechanism of action against Leishmania donovani

2020 ◽  
Author(s):  
Pragya Prasanna ◽  
Prakash Kumar ◽  
Saptarshi Mandal ◽  
Tanvi Patyal ◽  
Saurabh Kumar ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Biological Activity ◽  
Leishmania Donovani ◽  
Antioxidant Activities ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Drug Resistant ◽  
High Biological Activity ◽  
Resistant Strains ◽  
Drug Resistant Strains

Abstract Abstract Background – The synthesis of gold nanoparticles (GNPs) using drugs, synthetic and natural compounds, proteins, nucleic acids have become beneficial due to improved biological activity coupled with reduced cytotoxicity. In this regard, green synthesis of GNPs using plant extract enriched with flavonoids has shown increased attention due to improved antimicrobial efficacy, greater solubility, and better bioavailability of the flavonoid conjugated with GNPs. We have used 7, 8 dihydroxyflavone (DHF), a flavonoid that is enriched in plants and known for neurotropic and antioxidant activities, for the synthesis of GNP. In this report, we have investigated synthesis, characterization, and biological activity of DHF synthesized GNP against parasite Leishmania donovani . Results – Synthesized DHF functionalized GNPs (DHF-GNPs) are ~35 nm in size with zeta potential values of -34.1 mV, as observed from DLS studies. UV-Visible spectroscopy and FT-IR analysis confirms successful conjugation of DHF over GNP. TEM imaging shows uniform size and spherical distribution of NPs. Against L. donovani promastigotes IC 50 for DHF and DHF-GNP is ~140 µM and ~40 µM respectively. In ex vivo amastigote model, IC 50 for DHF and DHF-GNP is ~40 µM and ~22 µM respectively. Even with 1000 µM of DHF-GNP, cytotoxicity is only ~30% on THP1 cells indicating its high biocompatibility. In DHF-GNP treated parasites, activity of arginase decreases in a dose-dependent manner as evident from gene expression and enzyme-based studies. Supplementation of treated cells with ornithine, metabolite of arginase, shows the highest recovery from death. This indicates inhibition of arginase as the main reason for parasite death. Induction of IFN-γ and reduction IL-12 cytokine response shows a possible T h 1/T h 2-mediated cell death. Also, DHF and DHF-GNP are equally effective against sensitive and drug-resistant strains of L. donovani . Conclusion – Low cytotoxicity and high biological activity may provide an alternative but improved delivery of DHF whose solubility increases due to conjugation with GNP. Further efficacy against drug-resistant strains could be beneficial instead of conventional chemotherapy for leishmaniasis. Keywords : Functionalized gold nanoparticle, DHF, DHF-GNP, arginase inhibition, drug-resistant Parasite, iNOS activation

scholarly journals Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Riccardo Provenzani ◽  
Paola San-Martin-Galindo ◽  
Ghada Hassan ◽  
Ashenafi Legehar ◽  
Aleksi Kallio ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Total Biomass ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Concentration Dependent Manner ◽  
New Chemical Entities ◽  
Viable Bacteria ◽  
Conventional Antibiotics

AbstractBiofilms are multicellular communities of microorganisms that generally attach to surfaces in a self-produced matrix. Unlike planktonic cells, biofilms can withstand conventional antibiotics, causing significant challenges in the healthcare system. Currently, new chemical entities are urgently needed to develop novel anti-biofilm agents. In this study, we designed and synthesized a set of 2,4,5,6-tetrasubstituted pyrimidines and assessed their antibacterial activity against planktonic cells and biofilms formed by Staphylococcus aureus. Compounds 9e, 10d, and 10e displayed potent activity for inhibiting the onset of biofilm formation as well as for killing pre-formed biofilms of S. aureus ATCC 25923 and Newman strains, with half-maximal inhibitory concentration (IC50) values ranging from 11.6 to 62.0 µM. These pyrimidines, at 100 µM, not only decreased the number of viable bacteria within the pre-formed biofilm by 2–3 log10 but also reduced the amount of total biomass by 30–50%. Furthermore, these compounds were effective against planktonic cells with minimum inhibitory concentration (MIC) values lower than 60 µM for both staphylococcal strains. Compound 10d inhibited the growth of S. aureus ATCC 25923 in a concentration-dependent manner and displayed a bactericidal anti-staphylococcal activity. Taken together, our study highlights the value of multisubstituted pyrimidines to develop novel anti-biofilm agents.

scholarly journals Anti-Helicobacter pylori activity of acomplex mixture of Lactobacillus paracasei HP7 including the extract of Perilla frutescens var. acuta and Glycyrrhiza glabra

2020 ◽  
Vol 36 (1) ◽  
Author(s):  
Hyun-A Lee ◽  
Joo-Yun Kim ◽  
Jisoo Kim ◽  
Bora Nam ◽  
Okjin Kim
Keyword(s):  
Helicobacter Pylori ◽  
Complex Mixture ◽  
Perilla Frutescens ◽  
Glycyrrhiza Glabra ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Resistant Strains ◽  
H Pylori ◽  
Drug Resistant Strains

Abstract The effect of standard therapeutic strategies on Helicobacter pylori infection is diminished over time owing to the emergence of drug resistant strains. In this study, we would like to confirm the enhanced effect of L. paracasei HP7, which has been reported to exert antibacterial and gastric mucosal protective effects, in combination with Perilla frutescens var. acuta (P. frutescens)and Glycyrrhiza glabra (G. glabra) extracts. P. frutescens extract and G. glabra extract were found to inhibit the growth of H. pylori in a concentration-dependent manner, and the combination of L. paracasei HP7 and P. frutescens extract and G. glabra extract effectively inhibited H. pylori from attaching to AGS a gastric epithelial cells. Moreover, L. paracasei HP7 complex mixture containing P. frutescens and G. glabra extracts has been shown to inhibit H. pylori virulence genes such as AlpA, CagA, FlaA and UreA. When H. pylori-infected mice were administered a complex mixture of L. paracasei HP7 containing P. frutescens and G. glabra extract, the infection rate of H. pylori was significantly reduced. In addition, the L. paracasei HP7 complex mixture significantly reduced serum IL-8 levels and stomach inflammation in H. pylori infected mice. These results suggest that a complex mixture of L. paracasei HP7 containing P. frutescens and G. glabra extracts may be an alternative to treating diseases caused by H. pylori infection.

scholarly journals Omadacycline Potentiates Clarithromycin Activity Against Mycobacterium abscessus

2021 ◽  
Vol 12 ◽  
Author(s):  
Bui Thi Bich Hanh ◽  
Nguyen Thanh Quang ◽  
Yujin Park ◽  
Bo Eun Heo ◽  
Seunghyeon Jeon ◽  
...  
Keyword(s):  
Concentration Index ◽  
Inhibitory Concentration ◽  
Mycobacterium Abscessus ◽  
Respiratory Pathogen ◽  
Drug Resistant ◽  
Zebrafish Model ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Positive Effect

Mycobacterium abscessus is a difficult respiratory pathogen to treat, when compared to other nontuberculus mycobacteria (NTM), due to its drug resistance. In this study, we aimed to find a new clarithromycin partner that potentiated strong, positive, synergy against M. abscessus among current anti-M. abscessus drugs, including omadacycline, amikacin, rifabutin, bedaquiline, and cefoxitine. First, we determined the minimum inhibitory concentrations required of all the drugs tested for M. abscessus subsp. abscessus CIP104536T treatment using a resazurin microplate assay. Next, the best synergistic partner for clarithromycin against M. abscessus was determined using an in vitro checkerboard combination assay. Among the drug combinations evaluated, omadacycline showed the best synergistic effect with clarithromycin, with a fractional inhibitory concentration index of 0.4. This positive effect was also observed against M. abscessus clinical isolates and anti-M. abscessus drug resistant strains. Lastly, this combination was further validated using a M. abscessus infected zebrafish model. In this model, the clarithromycin-omadacyline regimen was found to inhibit the dissemination of M. abscessus, and it significantly extended the lifespan of the M. abscessus infected zebrafish. In summation, the synergy between two anti-M. abscessus compounds, clarithromycin and omadacycline, provides an attractive foundation for a new M. abscessus treatment regimen.

scholarly journals Synthesis of 7, 8 –dihydroxyflavone functionalized gold nanoparticles and its mechanism of action against Leishmania donovani

2021 ◽  
Author(s):  
Pragya Prasanna ◽  
Prakash Kumar ◽  
Saptarshi Mandal ◽  
Saurabh Kumar ◽  
Tanvi Payal ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Biological Activity ◽  
Leishmania Donovani ◽  
Dependent Manner ◽  
Gold Content ◽  
Drug Resistant ◽  
High Biological Activity ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Dose Dependent

Abstract Background – The synthesis of gold nanoparticles (GNPs) using drugs, synthetic and natural compounds, proteins, nucleic acids have become beneficial due to improved biological activity coupled with reduced cytotoxicity. In this regard, green synthesis of GNPs using plant extract enriched with flavonoids has shown increased attention due to improved antimicrobial efficacy, greater solubility, and better bioavailability of the flavonoid conjugated with GNPs. We have used 7, 8 dihydroxyflavone (DHF), a flavonoid that is enriched in plants and known for neurotropic and antioxidant activities, for the synthesis of GNP. In this report, we have investigated the synthesis, characterization, and biological activity of DHF synthesized GNP against the parasite Leishmania donovani. Results – Synthesized DHF functionalized GNPs (DHF-GNPs) are ~35 nm in size with zeta potential values of -34.1 mV, as observed from DLS studies. UV-Visible spectroscopy and FT-IR analysis confirm successful conjugation of DHF over GNP. TEM imaging shows the uniform size and spherical distribution of NPs. Against L. donovani promastigotes IC50 for DHF and DHF-GNP is ~120 µM and ~40 µM respectively. In ex vivo, amastigote model IC50 for DHF and DHF-GNP is ~40 µM and ~22 µM respectively. A dose-dependent increase of gold content as measured by atomic absorption spectroscopy (AAS) confirms the internalization of GNPs by macrophages. Even with 1000 µM of DHF-GNP, cytotoxicity is only ~30% compared to ~50% cytotoxicity of 40 µM c-GNP, on THP1 cells. It indicates high biocompatibility of DHF-GNP over c-GNP. In DHF-GNP treated parasites, the activity of arginase decreases in a dose-dependent manner as evident from gene expression and enzyme-based studies. Supplementation of treated cells with ornithine, metabolite of arginase, shows the highest recovery from death. This indicates inhibition of arginase as the main reason for parasite death. Induction of IFN-γ and reduction IL-12 cytokine response shows a possible Th1/Th2-mediated cell death. Also, DHF and DHF-GNP are equally effective against sensitive and drug-resistant strains of L. donovani. Conclusion – Low cytotoxicity and high biological activity may provide an alternative but improved delivery of DHF whose solubility increases due to conjugation with GNP. Further efficacy against drug-resistant strains could be beneficial instead of conventional chemotherapy for leishmaniasis.

scholarly journals Synthesis of 7, 8 –dihydroxyflavone functionalized gold nanoparticles and its mechanism of action against Leishmania donovani

2020 ◽  
Author(s):  
Pragya Prasanna ◽  
Prakash Kumar ◽  
Saptarshi Mandal ◽  
Tanvi Payal ◽  
Saurabh Kumar ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Biological Activity ◽  
Leishmania Donovani ◽  
Antioxidant Activities ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Drug Resistant ◽  
High Biological Activity ◽  
Resistant Strains ◽  
Drug Resistant Strains

Abstract Abstract Background – The synthesis of gold nanoparticles (GNPs) using drugs, synthetic and natural compounds, proteins, nucleic acids have become beneficial due to improved biological activity coupled with reduced cytotoxicity. In this regard, green synthesis of GNPs using plant extract enriched with flavonoids has shown increased attention due to improved antimicrobial efficacy, greater solubility, and better bioavailability of the flavonoid conjugated with GNPs. We have used 7, 8 dihydroxyflavone (DHF), a flavonoid that is enriched in plants and known for neurotropic and antioxidant activities, for the synthesis of GNP. In this report, we have investigated synthesis, characterization, and biological activity of DHF synthesized GNP against parasite Leishmania donovani . Results – Synthesized DHF functionalized GNPs (DHF-GNPs) are ~35 nm in size with zeta potential values of -34.1 mV, as observed from DLS studies. UV-Visible spectroscopy and FT-IR analysis confirms successful conjugation of DHF over GNP. TEM imaging shows uniform size and spherical distribution of NPs. Against L. donovani promastigotes IC 50 for DHF and DHF-GNP is ~140 µM and ~40 µM respectively. In ex vivo amastigote model, IC 50 for DHF and DHF-GNP is ~40 µM and ~22 µM respectively. Even with 1000 µM of DHF-GNP, cytotoxicity is only ~30% on THP1 cells indicating its high biocompatibility. In DHF-GNP treated parasites, activity of arginase decreases in a dose-dependent manner as evident from gene expression and enzyme-based studies. Supplementation of treated cells with ornithine, metabolite of arginase, shows the highest recovery from death. This indicates inhibition of arginase as the main reason for parasite death. Induction of IFN-γ and reduction IL-12 cytokine response shows a possible T h 1/T h 2-mediated cell death. Also, DHF and DHF-GNP are equally effective against sensitive and drug-resistant strains of L. donovani . Conclusion – Low cytotoxicity and high biological activity may provide an alternative but improved delivery of DHF whose solubility increases due to conjugation with GNP. Further efficacy against drug-resistant strains could be beneficial instead of conventional chemotherapy for leishmaniasis. Keywords : Functionalized gold nanoparticle, DHF, DHF-GNP, arginase inhibition, drug-resistant Parasite, iNOS activation

scholarly journals The Modulation of PCSK9 and LDLR by Supercritical CO2 Extracts of Mentha longifolia and Isolated Piperitone Oxide, an In Vitro Study

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3886
Author(s):  
Stefania Sut ◽  
Irene Ferrarese ◽  
Maria Giovanna Lupo ◽  
Nicola De Zordi ◽  
Elisa Tripicchio ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Density Lipoprotein ◽  
In Vitro Study ◽  
Volatile Constituent ◽  
Dependent Manner ◽  
Human Hepatoma Cell ◽  
Concentration Dependent Manner

In the present study the ability of supercritical carbon dioxide (SCO2) extracts of M. longifolia L. leaves to modulate low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression was evaluated in cultured human hepatoma cell lines Huh7 and HepG2. Two SCO2 extracts, one oil (ML-SCO2) and a semisolid (MW-SCO2), were subjected to detailed chemical characterization by mono- and bidimensional nuclear magnetic resonance (1D, 2D-NMR), gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS). Chemical analysis revealed significant amounts of fatty acids, phytosterols and terpenoids. ML-SCO2 was able to induce LDLR expression at a dose of 60 µg/mL in HuH7 and HepG2 cell lines. Furthermore, ML-SCO2 reduced PCSK9 secretion in a concentration-dependent manner in both cell lines. Piperitone oxide, the most abundant compound of the volatile constituent of ML-SCO2 (27% w/w), was isolated and tested for the same targets, showing a very effective reduction of PCSK9 expression. The overall results revealed the opportunity to obtain a new nutraceutical ingredient with a high amount of phytosterols and terpenoids using the SCO2 extraction of M. longifolia L., a very well-known botanical species used as food. Furthermore, for the first time we report the high activity of piperitone oxide in the reduction of PCSK9 expression.

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