scholarly journals Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum

2022 ◽  
Vol 11 ◽  
Author(s):  
Laís Pessanha de Carvalho ◽  
Sara Groeger-Otero ◽  
Andrea Kreidenweiss ◽  
Peter G. Kremsner ◽  
Benjamin Mordmüller ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Knowlesi ◽  
Rapid Onset ◽  
Multidrug Resistant ◽  
Antiplasmodial Activity ◽  
Onset Of Action ◽  
Streptomyces Antibioticus ◽  
Life Cycle Stages ◽  
Almost All

Boromycin is a boron-containing macrolide antibiotic produced by Streptomyces antibioticus with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug. Despite the success of artemisinin combination therapies, the current gold standard treatment, new alternatives are constantly needed due to the ability of malaria parasites to become resistant to almost all drugs that are in heavy clinical use. In vitro antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against Plasmodium falciparum and the zoonotic Plasmodium knowlesi. In contrast to tetracyclines, boromycin rapidly killed asexual stages of both Plasmodium species already at low concentrations (~ 1 nM) including multidrug resistant P. falciparum strains (Dd2, K1, 7G8). In addition, boromycin was active against P. falciparum stage V gametocytes at a low nanomolar range (IC50: 8.5 ± 3.6 nM). Assessment of the mode of action excluded the apicoplast as the main target. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite.

scholarly journals Deimmunized Lysostaphin Synergizes with Small-molecule Chemotherapies and Re-sensitizes MRSA to β-Lactam Antibiotics

2020 ◽  
pp. AAC.01707-20
Author(s):  
Yongliang Fang ◽  
Jack R. Kirsch ◽  
Liang Li ◽  
Seth A. Brooks ◽  
Spencer Heim ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Standard Of Care ◽  
Rapid Onset ◽  
Multidrug Resistant ◽  
Genetically Engineered ◽  
High Potency ◽  
Onset Of Action ◽  
New Antibiotics

There is an urgent need for novel agents to treat drug-resistant bacterial infections, such as multidrug-resistant Staphylococcus aureus (MRSA). Desirable properties for new antibiotics include high potency, narrow species selectivity, low propensity to elicit new resistance phenotypes, and synergy with standard of care (SOC) chemotherapies. Here, we describe analysis of the anti-MRSA potential exhibited by F12, an innovative anti-MRSA lysin that has been genetically engineered to evade detrimental antidrug immune responses in human patients. F12 possesses high potency and rapid onset of action, it has narrow selectivity against pathogenic Staphylococci, and it manifests synergy with numerous SOC antibiotics. Additionally, resistance to F12 and β-lactam antibiotics appears mutually exclusive, and importantly we provide evidence that F12 re-sensitizes normally resistant MRSA strains to β-lactams both in vitro and in vivo. These results suggest that combinations of F12 and SOC antibiotics could be a promising new approach to treating refractory S. aureus infections.

scholarly journals In vitro evaluation of verapamil and other modulating agents in Brazilian chloroquine-resistant Plasmodium falciparum isolates

2003 ◽  
Vol 36 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Carla M.S. Menezes ◽  
Karin Kirchgatter ◽  
Sílvia M. Di Santi ◽  
Carine Savalli ◽  
Fabíola G. Monteiro ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antipsychotic Drug ◽  
Antimalarial Drug ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Antiplasmodial Activity ◽  
Experimental Conditions ◽  
In Vitro Evaluation ◽  
Cardiovascular Therapy

Verapamil, was assayed to record its modulating effect upon Brazilian Plasmodium falciparum isolates resistant to chloroquine. Other cardiovascular drugs known to be modulating agents in resistant malaria and/or multidrug-resistant neoplasias, including nifedipine, nitrendipine, diltiazem and propranolol, were also evaluated. Concentrations similar to those for cardiovascular therapy were used in the in vitro microtechnique for antimalarial drug susceptibility. Intrinsic antiplasmodial activity was observed from the lowest concentrations without a significant modulating action. Other reported modulating agents, such as the antipsychotic drug trifluoperazine and the antidepressants desipramine and imipramine, demonstrated similar responses under the same experimental conditions. Results suggest a much higher susceptibility of Brazilian strains, as well as an indifferent behaviour in relation to modulating agents.

scholarly journals Antiplasmodial activity of Anthocleista djalonensis leaves extracts against clinical isolates of Plasmodium falciparum and multidrug resistant K1 strains

2020 ◽  
Vol 8 (3) ◽  
pp. 130-138
Author(s):  
Brice Kouakou Bla ◽  
Oléfongo Dagnogo ◽  
Rolland Gueyraud Kipré ◽  
Opportune Gogo Ballé ◽  
Jonhson David Trébissou ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistant ◽  
Traditional Healers ◽  
Antiplasmodial Activity ◽  
Clinical Isolates ◽  
Aqueous Extracts ◽  
Phytochemical Screening ◽  
Primary Health ◽  
Ethanolic Extracts

Information collected from nine (09) traditional healers in the Moronou village in the Department of Toumodi revealed that Anthocleista djanlonensis is regularly used by the population for primary health care in the processing of malaria. Evaluation of the In vitro antiplasmodial activity showed that the aqueous extracts inhibit growth of clinical isolates and chloroquinoresistant strains (K1) with IC50 of 8.29 µg/mL and 10.23 µg/mL while the ethanolic extracts had IC50 of 37.65 µg/mL and 46.07 µg/mL on the same strains respectively. Results of the In vitro antimalarial bioassay showed that aqueous extracts have promising antiplasmodial effects on clinical isolates and on Plasmodium falciparum multidrug resistant K1 strain (3 µg/mL <IC50 <15 µg/mL). Phytochemical screening revealed that the extracts contain mainly alkaloids, polyphenols, polyterpenes and flavonoids

Roxithromycin potentiates the effects of chloroquine and mefloquine on multidrug-resistant Plasmodium falciparum in vitro

2007 ◽  
Vol 115 (4) ◽  
pp. 387-392 ◽  
Author(s):  
T.H. Min ◽  
M.F.M. Khairul ◽  
J.H. Low ◽  
C.H. Che Nasriyyah ◽  
A. Noor A’shikin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistant

FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILMS OF PROCHLORPERAZINE MALEATE

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (12) ◽  
pp. 23-33
Author(s):  
R. Kanekar ◽  
◽  
P. M. Dandagi ◽  
A. P. Gadad
Keyword(s):  
Ex Vivo ◽  
Rapid Onset ◽  
Drug Release Profile ◽  
Onset Of Action ◽  
In Vitro Drug Release ◽  
Physico Chemical ◽  
Film Forming ◽  
Oral Films ◽  
Ex Vivo Study

The objective of the present study was to prepare and evaluate fast-dissolving oral films of prochlorperazine maleate (PCM), in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The solubility of the drug was increased by preparing inclusion complex with 2-hydroxypropyl-β-cyclodextrin (2HPβCD) and then incorporating it into the fast dissolving films. The fast-dissolving films of PCM were prepared by solvent casting method using different film forming polymers such as HPMC E15 and HPMC E5, either as single polymer or combination of the two. The film formulations were evaluated for various physico-chemical parameters. All formulations released more than 85% of the drug within 15 minutes. Formulation F4 showed best in vitro drug release profile. From the ex vivo study it was found that 94.79% of drug permeated through the porcine oral mucosa from the optimized formulation F4 within 60 mins.

PHYTOCHEMICAL INVESTIGATION AND ANTIMICROBIAL PROPERTIES OF DIOSCOREA BULBIFERA TUBER

2017 ◽  
Vol 10 (12) ◽  
pp. 317
Author(s):  
Dahiya P
Keyword(s):  
Antimicrobial Properties ◽  
Inhibition Zone ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Phytochemical Analysis ◽  
Phytochemical Investigation ◽  
Dioscorea Bulbifera ◽  
Acinetobacter Sp ◽  
Almost All

  Objective: The inhibitory properties of successive extracts from Dioscorea bulbifera (Dioscoreaceae) tubers have been evaluated for the presence of phytochemical constituents and antimicrobial efficacy against multidrug-resistant (MDR) clinical isolates was evaluated.Methods: The tuber of D. bulbifera was oven dried and extracted successively with n-hexane, chloroform, methanol, ethanol, and water. The antimicrobial potential of successive extracts against MDR isolates was studied by agar well-diffusion method. Qualitative phytochemical analysis was performed.Results: Qualitative phytochemical analysis demonstrated the presence of steroids, flavonoids, cardiac glycosides, saponins, and reducing sugars in almost all the extracts tested. Anthraquinones, phlobatanins, and tannins were not reported in any extracts tested. The in vitro antimicrobial activity of various solvents and water extracts of D. bulbifera was further investigated against ten MDR bacteria and three fungi, respectively. Aqueous and chloroform extracts were found to be more potent being capable of exerting significant inhibitory activities against the majority of the isolates such as Escherichia coli, Acinetobacter sp., Salmonella paratyphi, Klebsiella pneumoniae, and Candida albicans. The highest inhibitory activity was observed for K. pneumoniae with wide inhibition zone diameters (17 ± 0.15 mm), followed by E. coli 1(13 ± 0.11) mm, and Acinetobacter sp. (11 ± 0.12).Conclusion: Based on the present study, the extracts of D. bulbifera tubers have shown excellent activity against MDR microbial cultures tested. Further study is recommended for clinical evaluation, of the efficacy of crude extract in herbal medicine that can serve as a base for the development of novel potent drugs and phytomedicines.

scholarly journals In vitro Assessment of Antiplasmodial Activity and Acute Oral Toxicity of Dissotis rotundifolia Extracts and Fractions on Plasmodium falciparum Strains

2020 ◽  
pp. 8-19
Author(s):  
Rock Djehoue ◽  
Rafiou Adamou ◽  
Abdou Madjid O. Amoussa ◽  
Adande A. Medjigbodo ◽  
Anatole Laleye ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Acute Toxicity ◽  
Ethanolic Extract ◽  
Antiplasmodial Activity ◽  
Oral Toxicity ◽  
Aqueous Fraction ◽  
Vector Borne Diseases ◽  
Natural Substances ◽  
Study Laboratory

Aim: Dissotis rotundifolia were selected after an ethnopharmacological survey conducted on plants used traditionally for malaria treatment in South Benin, with the aim of discovering new natural active extracts against malaria parasites. Place and Duration of Study: Laboratory of Biochemistry and Bioactive Natural Substances, University of Abomey-Calavi (Benin)/ Laboratory of Infectious Vector Borne Diseases, Regional Institute of Public Health (Benin)/ Laboratoire d’Histologie, de Cytogénétique et d’Embryologie, Faculté des Sciences de la Santé (Benin). The study was conduct from October 2018 to June 2019 in Benin. Methodology: The antiplasmodial activity of the plant extracts was evaluated using the parasite lactate dehydrogenase (pLDH) immunodetection assay. The extract with the best antiplasmodial activity were used on Wistar rats for acute toxicity. Results: Ethanolic extract of Dissotis rotundifolia showed promising activity (Isolate: IC50 = 22.58 ± 1.12 µg/mL; 3D7: IC50 = 6.81 ± 0.85 µg/mL) on Plasmodium falciparum compared to the aqueous extract (Isolate: IC50 > 100 µg/mL; 3D7: IC50> 100 µg/mL). The aqueous fraction of D. rotundifolia exhibit highly potent activity against P. falciparum strain (Isolate: IC50 > 100 µg/mL μg/mL; 3D7: IC50 = 4.05 ± 0.72 μg/mL). Haemolytic effect of actives extracts and fractions is less than 5%. Ethanolic extract of D. rotundifolia revealed no obvious acute toxicity in rat up to the highest dose administered (2000 mg/kg). Conclusion: This study justifies traditional uses of D. rotundifolia against malaria. A bioguided fractionation of these extracts would identify molecules responsible for their antiplasmodial activity. Moreover, these results could lead to the design of improved traditional medicines in the basis of this plant.

scholarly journals Design, Development and Evaluation of Instant Release Oral Thin Films of Flunarizine

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Asfiya Fatima ◽  
Mamatha Tirunagari ◽  
Divya Theja Chilekampalli
Keyword(s):  
Thin Films ◽  
Drug Release ◽  
Hydroxypropyl Methylcellulose ◽  
Rapid Onset ◽  
In Vitro Dissolution ◽  
Design Development ◽  
Onset Of Action ◽  
Weight Variation ◽  
Accelerated Stability

The main objective of the present study was to prepare and evaluate the instant release oral thin films of Flunarizine, in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The instant release oral thin films of Flunarizine were prepared by solvent casting method using film forming polymer like Hydroxypropyl Methylcellulose E-15. The film was evaluated for various physicochemical parameters that include thickness, weight variation, folding endurance, tensile strength, drug content and in vitro drug release studies. No differences were observed in in vitro dissolution of drug from the formulated film F1-F9 as the film instantly gets wet by dissolution medium. The drug release for F5 formulations was about 98.1%. The accelerated stability studies for the optimized film formulations F5 were performed that indicates that the formulated instant release oral thin films were unaffected after initial and 3 months storage under accelerated conditions.

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