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 Tuberculosis drug resistance in Canada, 1998 to 2000

2001 ◽  
Vol 12 (3) ◽  
pp. 141-143
Author(s):  
Melissa D Phypers ◽  
Linda Panaro ◽  
Penny Nault
Keyword(s):  
World Health ◽  
Drug Resistant ◽  
First Line ◽  
International Union ◽  
The World ◽  
Resistant Strains ◽  
Health Organization ◽  
Global Threat ◽  
Drug Resistant Strains ◽  
And Control

The emergence of drug-resistant strains of tuberculosis (TB) is a global threat to TB prevention and control efforts. A recent study conducted by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease found strains of TB resistant to first-line anti-TB drugs in all countries surveyed (1). The WHO estimates that 50 million people are infected with strains of drug-resistant TB (2).

7,8-dihydroxyflavone-functionalized gold nanoparticles target the arginase enzyme of Leishmania donovani

Nanomedicine ◽  
2021 ◽  
Author(s):  
Pragya Prasanna ◽  
Prakash Kumar ◽  
Saptarshi Mandal ◽  
Tanvi Payal ◽  
Saurabh Kumar ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Leishmania Donovani ◽  
Drug Resistant ◽  
X Ray Diffraction ◽  
High Biological Activity ◽  
Transmission Electron ◽  
Resistant Strains ◽  
Low Cytotoxicity ◽  
Drug Resistant Strains ◽  
Parasite Leishmania

Aim: To analyze the efficacy and possible mechanism of action of 7,8-dihydroxyflavone (DHF) and DHF synthesized gold nanoparticles (GNPs) against the parasite Leishmania donovani. Methods: GNPs were synthesized using DHF and characterized by dynamic light scattering, ζ potential, Fourier transform infrared spectroscopy, transmission electron microscopy and x-ray diffraction. The efficacy of DHF and DHF-GNP were tested against sensitive and drug-resistant parasites. GNP uptake was measured on macrophages by atomic absorption spectroscopy. Results: DHF and DHF-GNP (∼35 nm) were equally effective against sensitive and drug-resistant strains and inhibited the arginase activity of parasites. Increased IFN-γ and reduced IL-12 cytokine response showed a Th1/Th2-mediated cell death in macrophages. Conclusion: The low cytotoxicity and high biological activity of DHF-GNP may be useful for chemotherapy of leishmaniasis.

scholarly journals What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae ?

2009 ◽  
Vol 7 (47) ◽  
pp. 905-919 ◽  
Author(s):  
Caroline Colijn ◽  
Ted Cohen ◽  
Christophe Fraser ◽  
William Hanage ◽  
Edward Goldstein ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Infectious Diseases ◽  
Multiple Infection ◽  
Drug Resistant ◽  
Host Interactions ◽  
Resistant Strains ◽  
Neutral Models ◽  
Drug Resistant Strains ◽  
And Control

The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance.

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 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 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 How can ecological urbanism promote human health?

2015 ◽  
Vol 8 (1) ◽  
pp. 77-95
Author(s):  
Laís Fajersztajn ◽  
Nilmara de Oliveira Alves ◽  
Micheline de Souza Zanotti Stagliorio Coelho ◽  
Mariana Matera Veras ◽  
Paulo Hilário Nascimento Saldiva
Keyword(s):  
Latin America ◽  
Health Outcomes ◽  
Disease Transmission ◽  
Drug Resistant ◽  
Special Issue ◽  
Adverse Health Outcomes ◽  
The World ◽  
Urban Settlements ◽  
Resistant Strains ◽  
Drug Resistant Strains

Abstract This special issue of URBE dedicated to Ecological Urbanism focuses on the role architects, landscape designers and urban planners can play in promoting healthier cities in Latin America. In this paper, we survey some of the empirical evidence that links the built environment with particular health outcomes. For many centuries, urban settlements were associated with adverse health outcomes, especially related to untreatable epidemics. As the science of disease transmission developed throughout the nineteenth century, the infrastructure of cities was transformed to promote improved public health. Significant gains were made, but in much of the world – Latin America included – urban health still remains a major challenge, all the more so as drug resistant strains of disease have become more prevalent. We believe Ecological Urbanism offers a promising framework for addressing these challenges. Distinguished by its integrated, multi-disciplinary foundation, Ecological Urbanism directly links both population and habitat health. This creates a natural opportunity for the design professions to play a more consequential role in shaping the health of urban settlements and, by extension, the regions they center.

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.

Invasive Shot Hole Borers Euwallacea fornicatus, E. kuroshio, and E. perbrevis (Coleoptera: Curculionidae: Scolytinae)

EDIS ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 7
Author(s):  
Demian F. Gomez ◽  
Jiri Hulcr ◽  
Daniel Carrillo
Keyword(s):  
South Africa ◽  
Invasive Species ◽  
Prevention And Control ◽  
Economic Impacts ◽  
Forest Resources ◽  
Economic Damage ◽  
Ambrosia Beetles ◽  
Invasive Insects ◽  
The World ◽  
And Control

Invasive species, those that are nonnative and cause economic damage, are one of the main threats to ecosystems around the world. Ambrosia beetles are some of the most common invasive insects. Currently, severe economic impacts have been increasingly reported for all the invasive shot hole borers in South Africa, California, Israel, and throughout Asia. This 7-page fact sheet written by Demian F. Gomez, Jiri Hulcr, and Daniel Carrillo and published by the School of Forest Resources and Conservation describes shot hole borers and their biology and hosts and lists some strategies for prevention and control of these pests. http://edis.ifas.ufl.edu/fr422

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