scholarly journals Evolution of Antibacterial Drug Screening Methods: Current Prospects for Mycobacteria

2021 ◽  
Vol 9 (12) ◽  
pp. 2562
Author(s):  
Clara M. Bento ◽  
Maria Salomé Gomes ◽  
Tânia Silva
Keyword(s):  
Rapid Development ◽  
Drug Susceptibility Testing ◽  
New Drugs ◽  
Host Cells ◽  
Screening Methods ◽  
Antibacterial Drug ◽  
Efficient Treatment ◽  
Wide Range

The increasing resistance of infectious agents to available drugs urges the continuous and rapid development of new and more efficient treatment options. This process, in turn, requires accurate and high-throughput techniques for antimicrobials’ testing. Conventional methods of drug susceptibility testing (DST) are reliable and standardized by competent entities and have been thoroughly applied to a wide range of microorganisms. However, they require much manual work and time, especially in the case of slow-growing organisms, such as mycobacteria. Aiming at a better prediction of the clinical efficacy of new drugs, in vitro infection models have evolved to closely mimic the environment that microorganisms experience inside the host. Automated methods allow in vitro DST on a big scale, and they can integrate models that recreate the interactions that the bacteria establish with host cells in vivo. Nonetheless, they are expensive and require a high level of expertise, which makes them still not applicable to routine laboratory work. In this review, we discuss conventional DST methods and how they should be used as a first screen to select active compounds. We also highlight their limitations and how they can be overcome by more complex and sophisticated in vitro models that reflect the dynamics present in the host during infection. Special attention is given to mycobacteria, which are simultaneously difficult to treat and especially challenging to study in the context of DST.

scholarly journals Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1125
Author(s):  
Raluca Nicu ◽  
Florin Ciolacu ◽  
Diana E. Ciolacu
Keyword(s):  
Rapid Development ◽  
Cellulose Nanofibrils ◽  
Functional Materials ◽  
Medical Applications ◽  
Bacterial Nanocellulose ◽  
Green Materials ◽  
Wide Range ◽  
In Vivo Cytotoxicity

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

scholarly journals Foeniculum vulgareMill: A Review of Its Botany, Phytochemistry, Pharmacology, Contemporary Application, and Toxicology

2014 ◽  
Vol 2014 ◽  
pp. 1-32 ◽  
Author(s):  
Shamkant B. Badgujar ◽  
Vainav V. Patel ◽  
Atmaram H. Bandivdekar
Keyword(s):  
Traditional Medicine ◽  
Scientific Evidence ◽  
New Drugs ◽  
Future Research ◽  
Foeniculum Vulgare ◽  
Wide Range ◽  
Research Findings ◽  
Valuable Compounds

Foeniculum vulgareMill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology ofFoeniculum vulgare. It also compiles available scientific evidence for the ethnobotanical claims and to identify gaps required to be filled by future research. Findings based on their traditional uses and scientific evaluation indicates thatFoeniculum vulgareremains to be the most widely used herbal plant. It has been used for more than forty types of disorders. Phytochemical studies have shown the presence of numerous valuable compounds, such as volatile compounds, flavonoids, phenolic compounds, fatty acids, and amino acids. Compiled data indicate their efficacy in severalin vitroandin vivopharmacological properties such as antimicrobial, antiviral, anti-inflammatory, antimutagenic, antinociceptive, antipyretic, antispasmodic, antithrombotic, apoptotic, cardiovascular, chemomodulatory, antitumor, hepatoprotective, hypoglycemic, hypolipidemic, and memory enhancing property.Foeniculum vulgarehas emerged as a good source of traditional medicine and it provides a noteworthy basis in pharmaceutical biology for the development/formulation of new drugs and future clinical uses.

scholarly journals Development of a Fluorescent Assay to Search New Drugs Using Stable tdTomato-Leishmania, and the Selection of Galangin as a Candidate With Anti-Leishmanial Activity

2021 ◽  
Vol 11 ◽  
Author(s):  
María Fernanda García-Bustos ◽  
Agustín Moya Álvarez ◽  
Cecilia Pérez Brandan ◽  
Cecilia Parodi ◽  
Andrea Mabel Sosa ◽  
...  
Keyword(s):  
Active Compound ◽  
Wild Strain ◽  
Fluorescence Assay ◽  
New Drugs ◽  
Lipid Inclusion ◽  
Screening Assay ◽  
Meglumine Antimoniate ◽  
Wide Range

Antimonials continue to be considered the first-line treatment for leishmaniases, but its use entails a wide range of side effects and serious reactions. The search of new drugs requires the development of methods more sensitive and faster than the conventional ones. We developed and validated a fluorescence assay based in the expression of tdTomato protein by Leishmania, and we applied this method to evaluate the activity in vitro of flavonoids and reference drugs. The pIR1SAT/tdTomato was constructed and integrated into the genome of Leishmania (Leishmania) amazonensis. Parasites were selected with nourseothricin (NTC). The relation of L. amaz/tc3 fluorescence and the number of parasites was determined; then the growth in vitro and infectivity in BALB/c mice was characterized. To validate the fluorescence assay, the efficacy of miltefosine and meglumine antimoniate was compared with the conventional methods. After that, the method was used to assess in vitro the activity of flavonoids; and the mechanism of action of the most active compound was evaluated by transmission electron microscopy and ELISA. A linear correlation was observed between the emission of fluorescence of L. amaz/tc3 and the number of parasites (r2 = 0.98), and the fluorescence was stable in the absence of NTC. No differences were observed in terms of infectivity between L. amaz/tc3 and wild strain. The efficacy of miltefosine and meglumine antimoniate determined by the fluorescence assay and the microscopic test showed no differences, however, in vivo the fluorescence assay was more sensitive than limiting dilution assay. Screening assay revealed that the flavonoid galangin (GAL) was the most active compound with IC50 values of 53.09 µM and 20.59 µM in promastigotes and intracellular amastigotes, respectively. Furthermore, GAL induced mitochondrial swelling, lipid inclusion bodies and vacuolization in promastigotes; and up-modulated the production of IL-12 p70 in infected macrophages. The fluorescence assay is a useful tool to assess the anti-leishmanial activity of new compounds. However, the assay has some limitations in the macrophage-amastigote model that might be related with an interfere of flavanol aglycones with the fluorescence readout of tdTomato. Finally, GAL is a promising candidate for the development of new treatment against the leishmaniasis.

scholarly journals Potential of 2-Chloro-N-(4-fluoro-3-nitrophenyl)acetamide Against Klebsiella pneumoniae and In Vitro Toxicity Analysis

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3959
Author(s):  
Laísa Cordeiro ◽  
Hermes Diniz-Neto ◽  
Pedro Figueiredo ◽  
Helivaldo Souza ◽  
Aleson Sousa ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Biological Activities ◽  
High Capacity ◽  
Pharmacokinetic Profile ◽  
In Vitro Toxicity ◽  
Antibacterial Drug ◽  
Wide Range ◽  
Good Potential

Klebsiella pneumoniae causes a wide range of community and nosocomial infections. The high capacity of this pathogen to acquire resistance drugs makes it necessary to develop therapeutic alternatives, discovering new antibacterial molecules. Acetamides are molecules that have several biological activities. However, there are no reports on the activity of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide. Based on this, this study aimed to investigate the in vitro antibacterial activity of this molecule on K. pneumoniae, evaluating whether the presence of the chloro atom improves this effect. Then, analyzing its antibacterial action more thoroughly, as well as its cytotoxic and pharmacokinetic profile, in order to contribute to future studies for the viability of a new antibacterial drug. It was shown that the substance has good potential against K. pneumoniae and the chloro atom is responsible for improving this activity, stabilizing the molecule in the target enzyme at the site. The substance possibly acts on penicillin-binding protein, promoting cell lysis. The analysis of cytotoxicity and mutagenicity shows favorable results for future in vivo toxicological tests to be carried out, with the aim of investigating the potential of this molecule. In addition, the substance showed an excellent pharmacokinetic profile, indicating good parameters for oral use.

scholarly journals Correspondence of In Vitro and In Vivo Fluconazole Dose-Response Curves for Cryptococcus neoformans

2005 ◽  
Vol 49 (8) ◽  
pp. 3297-3301 ◽  
Author(s):  
Robert A. Larsen ◽  
Madeline Bauer ◽  
Ann M. Thomas ◽  
Alejandro Sanchez ◽  
Diane Citron ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Dose Response ◽  
Response Curve ◽  
Drug Susceptibility Testing ◽  
Response Curves ◽  
In Vitro Susceptibility ◽  
Drug Concentrations ◽  
Wide Range

ABSTRACT We conducted in vitro experiments to evaluate the susceptibility of a clinical isolate of Cryptococcus neoformans to a wide range of concentrations of fluconazole. In vitro susceptibility was tested using broth macrodilution methods modified to provide a numeric count of viable organisms. The association between the quantitative in vitro response and fluconazole drug concentrations was estimated using local nonparametric regression. Regression analysis was used to assess the correspondence between the in vitro fluconazole concentration-response curve and the murine dose-response curve observed in our previously reported murine model. The regression model was then used to predict the murine response. There was a strong correspondence between in vitro measures of response to fluconazole alone and the previously reported biologic effects seen in the mouse. In vitro antifungal drug susceptibility testing can reliably predict the murine response to fluconazole.

scholarly journals Potentials of marine natural products against malaria, leishmaniasis, and trypanosomiasis parasites: a review of recent articles

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Justus Amuche Nweze ◽  
Florence N. Mbaoji ◽  
Yan-Ming Li ◽  
Li-Yan Yang ◽  
Shu-Shi Huang ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Marine Natural Products ◽  
Neglected Tropical Diseases ◽  
Marine Organisms ◽  
New Drugs ◽  
Screening Methods ◽  
Pharmaceutical Industries

Abstract Background Malaria and neglected communicable protozoa parasitic diseases, such as leishmaniasis, and trypanosomiasis, are among the otherwise called diseases for neglected communities, which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa, Asia, and the Americas. Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period, which have encouraged resistance. These have prompted many researchers to focus on finding new drugs that are safe, effective, and affordable from marine environments. The aim of this review was to show the diversity, structural scaffolds, in-vitro or in-vivo efficacy, and recent progress made in the discovery/isolation of marine natural products (MNPs) with potent bioactivity against malaria, leishmaniasis, and trypanosomiasis. Main text We searched PubMed and Google scholar using Boolean Operators (AND, OR, and NOT) and the combination of related terms for articles on marine natural products (MNPs) discovery published only in English language from January 2016 to June 2020. Twenty nine articles reported the isolation, identification and antiparasitic activity of the isolated compounds from marine environment. A total of 125 compounds were reported to have been isolated, out of which 45 were newly isolated compounds. These compounds were all isolated from bacteria, a fungus, sponges, algae, a bryozoan, cnidarians and soft corals. In recent years, great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds. Comparably, some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs. However, very few of these MNPs have a pharmaceutical destiny due to lack of the following: sustainable production of the bioactive compounds, standard efficient screening methods, knowledge of the mechanism of action, partnerships between researchers and pharmaceutical industries. Conclusions It is crystal clear that marine organisms are a rich source of antiparasitic compounds, such as alkaloids, terpenoids, peptides, polyketides, terpene, coumarins, steroids, fatty acid derivatives, and lactones. The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.

scholarly journals Repurposing Carvedilol as a Novel Inhibitor of the Trypanosoma cruzi Autophagy Flux That Affects Parasite Replication and Survival

2021 ◽  
Vol 11 ◽  
Author(s):  
Cynthia Vanesa Rivero ◽  
Santiago José Martínez ◽  
Paul Novick ◽  
Juan Agustín Cueto ◽  
Betiana Nebaí Salassa ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Parasite Burden ◽  
Drug Repurposing ◽  
Parasite Load ◽  
New Drugs ◽  
Host Cells ◽  
Whole Body ◽  
Parasite Replication

T. cruzi, the causal agent of Chagas disease, is a parasite able to infect different types of host cells and to persist chronically in the tissues of human and animal hosts. These qualities and the lack of an effective treatment for the chronic stage of the disease have contributed to the durability and the spread of the disease around the world. There is an urgent necessity to find new therapies for Chagas disease. Drug repurposing is a promising and cost-saving strategy for finding new drugs for different illnesses. In this work we describe the effect of carvedilol on T. cruzi. This compound, selected by virtual screening, increased the accumulation of immature autophagosomes characterized by lower acidity and hydrolytic properties. As a consequence of this action, the survival of trypomastigotes and the replication of epimastigotes and amastigotes were impaired, resulting in a significant reduction of infection and parasite load. Furthermore, carvedilol reduced the whole-body parasite burden peak in infected mice. In summary, in this work we present a repurposed drug with a significant in vitro and in vivo activity against T. cruzi. These data in addition to other pharmacological properties make carvedilol an attractive lead for Chagas disease treatment.

scholarly journals Preparation of serum capped silver nanoparticles for selective killing of microbial cells sparing host cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rehana Parveen ◽  
Prasanta Kumar Maiti ◽  
Nabendu Murmu ◽  
Alokmay Datta
Keyword(s):  
Silver Nanoparticles ◽  
Mammalian Cells ◽  
Vascular Endothelial Cells ◽  
Host Cells ◽  
Mice Model ◽  
Human Liver Cell ◽  
Wide Range ◽  
Stress Dependent

AbstractFollowing access into the cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The AgNP-Serum-18 when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis, and oxidative stress-dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is the least possibility of internalization into host cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascular endothelial cells. The presence of infection-specific antibodies in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by the in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open up wide-range therapeutic prospects of colloidal nanoparticles.

scholarly journals Preparation of Serum Capped Silver Nanoparticles for Selective Killing of Microbial Cells Sparing Host Cells

2021 ◽  
Author(s):  
Rehana Parveen ◽  
Prasanta Kumar Maiti ◽  
Nabendu Murmu ◽  
Alokmay Datta
Keyword(s):  
Silver Nanoparticles ◽  
Mammalian Cells ◽  
Host Cells ◽  
Mice Model ◽  
Human Liver Cell ◽  
Wide Range ◽  
Margin Of Safety ◽  
Stress Dependent

Abstract Following access into cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The serum capped silver nanoparticles when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis and oxidative stress dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is least possibility of internalization into host-cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascμμμar endothelial cells. Presence of infection specific antibody in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open-up wide-range therapeutic prospects of colloidal nanoparticles.

Antimicrobial Peptides from Musca Domestica Expressed in Escherichia coli

2012 ◽  
Vol 535-537 ◽  
pp. 2404-2408
Author(s):  
Bin Zeng
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Fusion Protein ◽  
Musca Domestica ◽  
Host Cells ◽  
Soluble Form ◽  
Wide Range ◽  
High Level

Cecropins are cationic molecules with a wide range of antimicrobial activities. The native peptide cecropins from Musca domestica (Md-Cec) have antimicrobial activity against both Gram-positive and Gram-negative bacteria. In the present study, cDNA fragments encoding both the Md-Cec-L (62aa) and Md-Cec-S (40 aa) peptides of Md-Cec were respectively expressed using the pMAL-c4x expression vector. High level expression of Md-Cec-L was achieved in Escherichia coli, while expression of Md-Cec-S failed to reach a decent level due to its high level of toxicity to the host cells. Md-Cec-L was expressed as a soluble form using a maltose binding protein (MBP) system, whose product is a MBP-tagged fusion protein, and separated with the carrier amyrose resin. Heterologous expression in E. coli and antimicrobial activity assays showed that both the recombinant fusion protein Md-Cec-L and Md-Cec-S have exhibited antimicrobial activity in vivo; and Md-Cec-L also exhibited antimicrobial activity in vitro. Md-Cec has the potential to be developed as a novel type of antimicrobial drug or food preservative.

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