scholarly journals Overcoming the Prokaryote/Eukaryote Barrier in Tuberculosis Treatment: A Prospect for the Repurposing and Use of Antiparasitic Drugs

2021 ◽  
Vol 9 (11) ◽  
pp. 2335
Author(s):  
José Manuel Ezquerra-Aznárez ◽  
Pedro E. Almeida da Silva ◽  
José A. Aínsa
Keyword(s):  
Antimicrobial Agents ◽  
Low Cost ◽  
Tuberculosis Treatment ◽  
Parasitic Infections ◽  
Potential Contributor ◽  
Parasitic Activity ◽  
Antiparasitic Drugs ◽  
Approved Drugs ◽  
Tuberculosis Therapy ◽  
Derivatives Of

Antimicrobial resistance, the so-called silent pandemic, is pushing industry and academia to find novel antimicrobial agents with new mechanisms of action in order to be active against susceptible and drug-resistant microorganisms. In the case of tuberculosis, the need of novel anti-tuberculosis drugs is specially challenging because of the intricate biology of its causative agent, Mycobacterium tuberculosis. The repurposing of medicines has arisen in recent years as a fast, low-cost, and efficient strategy to identify novel biomedical applications for already approved drugs. This review is focused on anti-parasitic drugs that have additionally demonstrated certain levels of anti-tuberculosis activity; along with this, natural products with a dual activity against parasites and against M. tuberculosis are discussed. A few clinical trials have tested antiparasitic drugs in tuberculosis patients, and have revealed effective dose and toxicity issues, which is consistent with the natural differences between tuberculosis and parasitic infections. However, through medicinal chemistry approaches, derivatives of drugs with anti-parasitic activity have become successful drugs for use in tuberculosis therapy. In summary, even when the repurposing of anti-parasitic drugs for tuberculosis treatment does not seem to be an easy job, it deserves attention as a potential contributor to fuel the anti-tuberculosis drug pipeline.

scholarly journals Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3193
Author(s):  
Christina Pfab ◽  
Luisa Schnobrich ◽  
Samir Eldnasoury ◽  
André Gessner ◽  
Nahed El-Najjar
Keyword(s):  
Clinical Trials ◽  
Antimicrobial Agents ◽  
Large Body ◽  
Drug Repurposing ◽  
Extensive Discussion ◽  
Attrition Rates ◽  
Beneficial Effects ◽  
Stage Of Development ◽  
Development Costs ◽  
Approved Drugs

The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.

scholarly journals SYNTHESIS AND ANTIMICROBIAL EVALUATION OF QUINAZOLINONE PEPTIDE DERIVATIVES

2017 ◽  
Vol 10 (16) ◽  
pp. 7 ◽  
Author(s):  
Bhupinder Kapoor ◽  
Arshid Nabi ◽  
Reena Gupta ◽  
Mukta Gupta
Keyword(s):  
Antibacterial Activity ◽  
Amino Acid ◽  
Antimicrobial Agents ◽  
Methyl Esters ◽  
Standard Drug ◽  
Amino Acid Peptide ◽  
Chemical Structures ◽  
1H Nuclear Magnetic Resonance ◽  
Peptide Derivatives ◽  
Derivatives Of

  Objective: The increased microbial resistance against commercially available drugs initiated the development of novel and safe antimicrobial agents in last few decades. In this view, a series of amino acid/dipeptide derivatives of quinazolin-3(4H)-one was synthesized and was evaluated for their antimicrobial potential.Method: Synthesis of amino acid/peptide derivatives were carried out by coupling 5-(2-(2-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)-2-hydroxy benzoic acid with amino acid/dipeptide methyl esters in the presence of dicyclohexylcarbodiimide and N-methylmorpholine. The chemical structures of synthesized compounds were characterized by 1H nuclear magnetic resonance and infrared spectroscopy and were screened for antibacterial activity by disc diffusion method.Results: All the synthesized derivatives exhibited moderate to significant antibacterial activity against both Gram-positive and Gram-negative bacteria. The potency of compound 5d was comparable to standard drug ciprofloxacin in all the strains of bacteria used. The compound 5a was found to be more active against Streptococcus pyogenes and Staphylococcus aureus while compound 5c against Pseudomonas aeruginosa and Escherichia coli. Conclusion: Peptide derivatives of quinazolinone are promising antimicrobial agent and can be used for the synthesis of other novel compounds.

scholarly journals Microbial Transformations of Isophorone by Alternaria alternata and Neurospora crassa

2013 ◽  
Vol 8 (1) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Ismail Kiran ◽  
Özge Özşen ◽  
Turgay Çelik ◽  
Semra İlhan ◽  
Bükay Yenice Gürsu ◽  
...  
Keyword(s):  
Neurospora Crassa ◽  
Alternaria Alternata ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Anti Oxidant ◽  
Agar Dilution ◽  
Important Field ◽  
Pharmacology And Toxicology ◽  
Derivatives Of

Isophorone (3,5,5-trimethyl-2-cyclohexen-1-one), a monoterpene, and the structurally related 1,8-cineole and camphor, have demonstrated a protective effect against cancer, biological activity against a variety of microorganisms, and anti-oxidant properties. The derivatization of isophorone is, therefore, an important field of xenobiochemistry, pharmacology and toxicology. The aim of this study was to obtain derivatives of isophorone through microbial biotransformation and evaluate the biotransformation metabolites as potential antimicrobial agents. Incubation of isophorone with the fungi Alternaria alternata and Neurospora crassa afforded 4α-hydroxy- and 7-hydroxy-isophorone as transformation metabolites. The antimicrobial activities of isophorone and the metabolites were evaluated in vitro both by using agar dilution and microdilution methods. However, no significant antibacterial activity was observed when compared with those of standard substances.

scholarly journals Toxin Neutralization Using Alternative Binding Proteins

Toxins ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 53 ◽  
Author(s):  
Timothy Jenkins ◽  
Thomas Fryer ◽  
Rasmus Dehli ◽  
Jonas Jürgensen ◽  
Albert Fuglsang-Madsen ◽  
...  
Keyword(s):  
Binding Protein ◽  
Low Cost ◽  
Protein Scaffolds ◽  
Comprehensive Overview ◽  
Alternative Protein ◽  
Human Proteins ◽  
Cost Of Production ◽  
High Level ◽  
Antibody Derivatives ◽  
Derivatives Of

Animal toxins present a major threat to human health worldwide, predominantly through snakebite envenomings, which are responsible for over 100,000 deaths each year. To date, the only available treatment against snakebite envenoming is plasma-derived antivenom. However, despite being key to limiting morbidity and mortality among snakebite victims, current antivenoms suffer from several drawbacks, such as immunogenicity and high cost of production. Consequently, avenues for improving envenoming therapy, such as the discovery of toxin-sequestering monoclonal antibodies against medically important target toxins through phage display selection, are being explored. However, alternative binding protein scaffolds that exhibit certain advantages compared to the well-known immunoglobulin G scaffold, including high stability under harsh conditions and low cost of production, may pose as possible low-cost alternatives to antibody-based therapeutics. There is now a plethora of alternative binding protein scaffolds, ranging from antibody derivatives (e.g., nanobodies), through rationally designed derivatives of other human proteins (e.g., DARPins), to derivatives of non-human proteins (e.g., affibodies), all exhibiting different biochemical and pharmacokinetic profiles. Undeniably, the high level of engineerability and potentially low cost of production, associated with many alternative protein scaffolds, present an exciting possibility for the future of snakebite therapeutics and merit thorough investigation. In this review, a comprehensive overview of the different types of binding protein scaffolds is provided together with a discussion on their relevance as potential modalities for use as next-generation antivenoms.

scholarly journals Green and efficient three-component synthesis of 4H-pyran catalysed by CuFe 2 O 4 @starch as a magnetically recyclable bionanocatalyst

2020 ◽  
Vol 7 (7) ◽  
pp. 200385
Author(s):  
Maryam Kamalzare ◽  
Mohammad Bayat ◽  
Ali Maleki
Keyword(s):  
Low Cost ◽  
Environmentally Benign ◽  
Pharmaceutical Chemistry ◽  
X Ray Diffraction ◽  
Natural Polymers ◽  
X Ray ◽  
Benign Nature ◽  
Catalytic Behaviour ◽  
Work Up ◽  
Derivatives Of

The development of simple, practical and inexpensive catalysis systems using natural materials is one of the main goals of pharmaceutical chemistry as well as green chemistry. Owing to the ability of easy separation of nanocatalyst, those goals could be approached by applying heterogeneous bionanocatalyst in combination with magnetic nanoparticles. Starch is one of the most abundant natural polymers; therefore, preparing bionanocatalyst from starch is very valuable as starch is largely available and inexpensive. An ecologically benign and efficacious heterogeneous nanocatalyst was prepared based on a biopolymer, and its attributes and morphology were specified by using Fourier transform infrared spectra, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), thermal analysis and vibrating sample magnetometer measurements; followed by studying catalytic behaviour of bionanocomposite in a multicomponent reaction to synthesize of 4H-pyran derivatives. 4H-pyran is extremely valuable in pharmaceutical chemistry, and the development of methods for synthesis of different derivatives of 4H-pyran is momentous. Revealing environmentally benign nature, mild condition, easy work-up, low cost and non-toxicity are some of the advantages of this protocol. Besides, the bionanocomposite was recovered using an external magnetic bar and could be re-used at least six times with no further decrease in its catalytic activity.

scholarly journals Preparation and Hydro-Lipophilic Properties of Selected Novel Chlorinated and Brominated N-Arylcinnamamides

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 11
Author(s):  
Tomas Strharsky ◽  
Timotej Jankech ◽  
Jiri Kos ◽  
Kristina Maricakova ◽  
Andrea Pramukova ◽  
...  
Keyword(s):  
High Performance ◽  
Chemical Structure ◽  
Antimicrobial Agents ◽  
Reversed Phase ◽  
Log P ◽  
Organic Modifier ◽  
Chromatography Method ◽  
P Values ◽  
Liquid Chromatography Method ◽  
Derivatives Of

A series of six di- and tri-halogenated N-arylcinnamanilides designed as anti-inflammatory and antimicrobial agents was prepared and characterized. Since it is known that lipophilicity significantly influences the biological activity of compounds, the hydro-lipophilic properties of these di- and tri-substituted N-arylcinnamanilides were investigated in the study. All the discussed derivatives of cinnamic acid were analyzed using the reversed-phase high performance liquid chromatography method to measure lipophilicity. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. In the present study, the correlations between the logarithm of the capacity factor k and log P/Clog P values calculated in various ways as well as the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.

scholarly journals Highly Asymmetric Reduction of New Benzofuryl and Benzothiophenyl α-Amino Ketones

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 49
Author(s):  
Agnieszka Tafelska-Kaczmarek ◽  
Marcin Kwit ◽  
Bartosz Stasiak
Keyword(s):  
High Performance ◽  
Asymmetric Reduction ◽  
Theoretical Calculations ◽  
Transfer Hydrogenation ◽  
Central Position ◽  
Chiral Hplc ◽  
Naturally Occurring ◽  
Approved Drugs ◽  
High Yields ◽  
Derivatives Of

Heterocyclic compounds play an important role in medicinal chemistry and occupy a central position in synthetic organic chemistry. Both benzofuran and benzothiophene are considered as very important structures due to their diverse biological and pharmacological profile. Many clinically approved drugs are synthetic and naturally occurring substituted benzofuryl and benzothiophenyl derivatives in conjunction with other heterocycles. Therefore, a new series of α-amino ketone (containing various azole rings) derivatives of benzofuran and benzothiophene are synthesized and subjected to the transfer hydrogenation with formic acid, catalyzed by RhCl[(R,R)-TsDPEN](C5Me5). The corresponding optically active β-amino alcohols are obtained in high yields and excellent enantioselectivities (93%–99%), as determined by chiral HPLC (high-performance liquid chromatography). The absolute configuration of the products is confirmed by means of ECD (electronic circular dichroism) spectroscopy, supported by theoretical calculations.

scholarly journals A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization

2020 ◽  
Vol 21 (18) ◽  
pp. 6952
Author(s):  
Bruna Agrillo ◽  
Yolande T. R. Proroga ◽  
Marta Gogliettino ◽  
Marco Balestrieri ◽  
Rosarita Tatè ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
De Novo ◽  
Low Cost ◽  
Functional Characterization ◽  
Human Keratinocytes ◽  
Minimal Bactericidal Concentration ◽  
Microbial Spoilage ◽  
Structural Resistance

Antimicrobial peptides (AMPs) are excellent candidates to fight multi-resistant pathogens worldwide and are considered promising bio-preservatives to control microbial spoilage through food processing. To date, designing de novo AMPs with high therapeutic indexes, low-cost synthesis, high resistance, and bioavailability, remains a challenge. In this study, a novel decapeptide, named RiLK1, was rationally designed starting from the sequence of the previously characterized AMP 1018-K6, with the aim of developing short peptides, and promoting higher selectivity over mammalian cells, antibacterial activity, and structural resistance under different salt, pH, and temperature conditions. Interestingly, RiLK1 displayed a broad-spectrum of bactericidal activity against Gram-positive and Gram-negative bacteria, including multidrug resistant clinical isolates of Salmonella species, with Minimal Bactericidal Concentration (MBC) values in low micromolar range, and it was effective even against two fungal pathogens with no evidence of cytotoxicity on human keratinocytes and fibroblasts. Moreover, RiLK1-activated polypropylene films were revealed to efficiently prevent the growth of microbial spoilage, possibly improving the shelf life of fresh food products. These results suggested that de novo designed peptide RiLK1 could be the first candidate for the development of a promising class of decameric and multitask antimicrobial agents to overcome drug-resistance phenomena.

scholarly journals Recycling Old Antibiotics with Ionic Liquids

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 578
Author(s):  
Cristina Prudêncio ◽  
Mónica Vieira ◽  
Seppe Van der Auweraer ◽  
Ricardo Ferraz
Keyword(s):  
Ionic Liquids ◽  
Pharmaceutical Industry ◽  
Antimicrobial Agents ◽  
Phage Therapy ◽  
Low Cost ◽  
Therapeutic Strategies ◽  
Pathogenic Microorganisms ◽  
Antibacterial Resistance ◽  
Resistant Strains ◽  
Social Habits

Antibiotics are considered one of the great “miracles” of the 20th century. Now in the 21st century in the post-antibiotic era, the miracle is turning into a nightmare, due to the growing problem of the resistance of microorganisms to classic antimicrobials and the non-investment by the pharmaceutical industry in new antimicrobial agents. Unfortunately, the current COVID-19 pandemic has demonstrated the global risks associated with uncontrolled infections and the various forms of impact that such a pandemic may have on the economy and on social habits besides the associated morbidity and mortality. Therefore, there is an urgent need to recycle classic antibiotics, as is the case in the use of ionic liquids (ILs) based on antibiotics. Thus, the aim of the present review is to summarize the data on ILs, mainly those with antimicrobial action and especially against resistant strains. The main conclusions of this article are that ILs are flexible due to their ability to modulate cations and anions as a salt, making it possible to combine the properties of both and multiplying the activity of separate cations and anions. Also, these compounds have low cost methods of production, which makes it highly attractive to explore them, especially as antimicrobial agents and against resistant strains. ILs may further be combined with other therapeutic strategies, such as phage or lysine therapy, enhancing the therapeutic arsenal needed to fight this worldwide problem of antibacterial resistance. Thus, the use of ILs as antibiotics by themselves or together with phage therapy and lysine therapy are promising alternatives against pathogenic microorganisms, and may have the possibility to be used in new ways in order to restrain uncontrolled infections.

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