scholarly journals Synergistic Antimycobacterial Actions ofKnowltonia vesicatoria(L.f) Sims

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Antoinette Labuschagné ◽  
Ahmed A. Hussein ◽  
Benjamín Rodríguez ◽  
Namrita Lall
Keyword(s):  
South African ◽  
Inhibitory Concentration ◽  
Ethanol Extract ◽  
Antimycobacterial Activity ◽  
First Report ◽  
Pelargonium Sidoides ◽  
Resistant Strains ◽  
African Plants ◽  
Drug Resistant Strains ◽  
Euclea Natalensis

Euclea natalensisA.DC.,Knowltonia vesicatoria(L.f) Sims, andPelargonium sidoidesDC. are South African plants traditionally used to treat tuberculosis. Extracts from these plants were used in combination with isoniazid (INH) to investigate the possibility of synergy with respect to antimycobacterial activity. The ethanol extract ofK. vesicatoriawas subjected to fractionation to identify the active compounds. The activity of theKnowltoniaextract remained superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0 μg/mL againstMycobacterium smegmatisand an MIC of 50.00 μg/mL againstM. tuberculosis. TheK. vesicatoriaextract was tested against two different drug-resistant strains ofM. tuberculosis, which resulted in an MIC of 50.00 μg/mL on both strains. The combination ofK. vesicatoriawith INH exhibited the best synergistic antimycobacterial activity with a fractional inhibitory concentration index of 0.25 (a combined concentration of 6.28 μg/mL). A fifty percent inhibitory concentration of this combination against U937 cells was 121.0 μg/mL. Two compounds, stigmasta-5,23-dien-3-ol (1) and 5-(hydroxymethyl)furan-2(5H)-one (2), were isolated fromK. vesicatoriaas the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1) was active against drug-sensitiveM. tuberculosiswith an MIC of 50.00 μg/mL.

scholarly journals Investigation of the acaricidal activity of the acetone and ethanol extracts of 12 South African plants against the adult ticks of Rhipicephalus turanicus

2017 ◽  
Vol 84 (1) ◽  
Author(s):  
Gerda Fouche ◽  
Bellonah M. Sakong ◽  
Olubukola T. Adenubi ◽  
Jean Paul Dzoyem ◽  
Vinny Naidoo ◽  
...  
Keyword(s):  
South African ◽  
Ethanol Extract ◽  
Immersion Test ◽  
Acaricidal Activity ◽  
Contact Method ◽  
Cleome Gynandra ◽  
Whole Plant ◽  
African Plants ◽  
Ethanol Extracts ◽  
Acetone Extracts

The acaricidal activity of acetone and ethanol extracts of 12 plant species was evaluated using the contact method on Rhipicephalus turanicus (Acari: Ixodidae) ticks at an initial concentration of 20% (200 mg/mL). Eight of the 12 plants had mortality greater than 50% and the acetone extracts had better acaricidal activity than the ethanol extracts. The acetone extract of Calpurnia aurea (leaves and flowers) had the highest corrected mortality (CM) of 92.2% followed by Schkuhria pinnata (whole plant) with a CM of 88.9%, Ficus sycomorus (bark and stems) 86.7% and Senna italica subsp. arachoides (roots, leaves and fruits) 83.3%. Selected extracts were tested at five different concentrations using the adult immersion test. From dose–response assays, EC<sub>50</sub> values of 61.82 mg/mL, 115.21 mg/mL and 161.02 mg/mL were obtained for the acetone extracts of S. pinnata (whole plant), S. italica subsp. arachoides (roots, leaves and fruits) and C. aurea (leaves and flowers) respectively. The ethanol extract of Monsonia angustifolia (whole plant) had the highest CM of 97.8% followed by S. pinnata (whole plant) with a CM of 86.7%, C. aurea (leaves and flowers) 81.1% and Cleome gynandra (leaves) 77.8%. There is potential for the development of environmentally benign botanicals as natural acaricides against R. turanicus.

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 Effects of Tormentic Acid and the Extracts from Callistemon citrinus on the Production of Extracellular Proteases by Staphylococcus aureus

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Rumbidzai Mashezha ◽  
Molly Mombeshora ◽  
Stanley Mukanganyama
Keyword(s):  
Staphylococcus Aureus ◽  
Ethanol Extract ◽  
Extracellular Protease ◽  
Protease Production ◽  
Extracellular Proteases ◽  
Therapeutic Molecules ◽  
Antibacterial Susceptibility ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Tormentic Acid

Staphylococcus aureus is among the common nosocomial pathogens. Antibiotics have been used to treat S. aureus infections. However, there has been increased mortality associated with drug-resistant strains of S. aureus. Extracellular proteases have been implicated to be responsible for the transition of S. aureus from an adhesive pathogen to an invasive pathogen. The development of resistant strains has necessitated the search for new sources of drugs. Plants have been traditionally used as sources of therapeutic molecules. The objective of this study was to determine the effect of tormentic acid and the extracts from Callistemon citrinus on the production of extracellular proteases by S. aureus. The broth microdilution antibacterial susceptibility assay was used to determine the antibacterial effects of tormentic acid and the extracts on S. aureus. Both extracts showed a minimum inhibitory concentration (MIC) value of 50 μg/ml. The water : ethanol (50 : 50) and the dichloromethane : methanol (50 : 50) extracts were found to be bactericidal against S. aureus at a concentration of 100 μg/ml and 50 μg/ml, respectively. The effect of tormentic acid and extracts on extracellular protease production was investigated using the protease assay. A zone of proteolytic activity (Pr) was measured as the ratio of the diameter of the colony to the total diameter of colony plus zone of hydrolysis. The extracts reduced the production of extracellular proteases, while tormentic acid completely inhibited the production of extracellular proteases by S. aureus. The Pr value for tormentic acid was found to be 1. The Pr values of the dichloromethane : methanol extract and the water : ethanol extract were 0.92 and 0.84, respectively. In conclusion, tormentic acid was shown to inhibit extracellular protease production; therefore, there is need to explore its use in antivirulence therapy to combat S. aureus infections.

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 Synthesis of Antimycobacterial Agents that Harness Mycothiol and Cysteine conjugate β-lyase Metabolic Pathways

2021 ◽  
Author(s):  
◽  
Scott W. Riordan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Antimycobacterial Activity ◽  
New Drugs ◽  
Bacillus Calmette Guerin ◽  
Antimycobacterial Agents ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Related Compounds ◽  
Synthetic Target

<p>Mycobacterium tuberculosis kills approximately two million people each year and is second only to HIV/AIDs in terms of death from infectious disease. The most pertinent problem in regards to Mycobacterium tuberculosis today is the increasing prevalence of drug resistant strains. Thus, there is a great need for the development of new drugs with novel targets. This thesis aimed to address this problem by synthesizing a compound that could exploit the mycothiol detoxification pathway, unique to Mycobacterium, in order to cause cell death, through the release of a harmful halothioketene.  The research described herein involved the successful synthesis of the desired mycothiol analogue, along with three other related compounds. The target compounds were synthesised via protection of N-acetyl glucosamine, followed by thioglycosidation with cyclohexane thiol. Subsequent deprotection and coupling to Boc protected Strichlorovinyl cysteine provided access to the synthetic target and its β-anomer, as well as their Boc protected precursors.  The original synthetic target demonstrated weak antimycobacterial activity against Mycobacterium smegmatis and an encouraging sub 100 μM MIC against Mycobacterium bovis derived Bacillus Calmette–Guérin. Unexpectedly the beta anomer of the synthetic target also displayed antimycobacterial activity against Bacillus Calmette–Guérin (MIC 125 - 250 μM). All compounds proved to be active against HL60 cells (16-114 μM).  Whilst further work is required to improve efficacy, the work presented here demonstrates the potential of these compounds as leads for the generation of new antimycobacterial agents.</p>

scholarly journals Antimicrobial susceptibility and minimal inhibitory concentration of bacteria isolated from the eyes of dogs with keratoconjunctivitis sicca

2019 ◽  
Vol 39 (9) ◽  
pp. 757-763
Author(s):  
Carolina S.G. Pereira ◽  
Luís Felipe C. Zulim ◽  
Rogério Giuffrida ◽  
Aline G. Cruz ◽  
Bruna T.D. Foglia ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Inhibitory Concentration ◽  
Keratoconjunctivitis Sicca ◽  
Polymyxin B ◽  
Control Group ◽  
Aerobic Culture ◽  
Staphylococcus Intermedius ◽  
Antimicrobial Susceptibility Profile ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT: The objective of this study was to evaluate the antimicrobial susceptibility profile of bacteria isolated from the eyes of dogs with keratoconjunctivitis sicca (KCS). We evaluated 65 dogs diagnosed with KCS and 30 healthy dogs (Control Group). Conjunctival swab samples were collected after KCS was diagnosed. Microbiological examinations were performed, including aerobic culture, antimicrobial susceptibility testing and minimum inhibitory concentration (MIC) determination for chloramphenicol, tobramycin, ofloxacin and moxifloxacin. MICs of the fifteen most resistant strains of Staphylococcus pseudintermedius (Staphylococcus intermedius Group, SIG) and the fifteen most resistant strains of gram-negative bacteria were determined. By percentage, the microorganisms exhibited the highest susceptibility to polymyxin B, tobramycin and chloramphenicol and the lowest to tetracycline. Three multi-drug-resistant strains of SIG were detected: one displayed isolated susceptibility to cefazolin, another to vancomycin, and another to polymyxin B and amikacin. The species of bacteria isolated from the eyes of dogs with KCS presented variable susceptibility to the antibiotics tested. We found evidence of the emergence of quinolone-resistant strains of SIG and further evidence of increased ocular prevalence. These findings reinforce the need to identify the bacteria involved and their antimicrobial susceptibility profile, as secondary infections can serve as exacerbating and perpetuating factors in KCS.

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