Natural Occurrence in Venomous Arthropods of Antimicrobial Peptides Active against Protozoan Parasites

Arthropoda is a phylum of invertebrates that has undergone remarkable evolutionary radiation, with a wide range of venomous animals. Arthropod venom is a complex mixture of molecules and a source of new compounds, including antimicrobial peptides (AMPs). Most AMPs affect membrane integrity and produce lethal pores in microorganisms, including protozoan pathogens, whereas others act on internal targets or by modulation of the host immune system. Protozoan parasites cause some serious life-threatening diseases among millions of people worldwide, mostly affecting the poorest in developing tropical regions. Humans can be infected with protozoan parasites belonging to the genera Trypanosoma, Leishmania, Plasmodium, and Toxoplasma, responsible for Chagas disease, human African trypanosomiasis, leishmaniasis, malaria, and toxoplasmosis. There is not yet any cure or vaccine for these illnesses, and the current antiprotozoal chemotherapeutic compounds are inefficient and toxic and have been in clinical use for decades, which increases drug resistance. In this review, we will present an overview of AMPs, the diverse modes of action of AMPs on protozoan targets, and the prospection of novel AMPs isolated from venomous arthropods with the potential to become novel clinical agents to treat protozoan-borne diseases.

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Novel Dipeptides Bearing Sulfonamide as Antimalarial and Antitrypanosomal agents: Synthesis and Molecular Docking

Medicinal Chemistry ◽

10.2174/1573406417666210604101201 ◽

2021 ◽

Vol 17 ◽

Author(s):

Ogechi Chinelo Ekoh ◽

Uchechukwu Okoro ◽

David Ugwu ◽

Rafat Ali ◽

Sunday Okafor ◽

...

Keyword(s):

Molecular Docking ◽

Condensation Reaction ◽

Drug Resistant ◽

Protozoan Parasites ◽

Diminazene Aceturate ◽

Standard Drug ◽

Tropical Regions ◽

Haematological Analysis ◽

New Compounds

Objective: Currently, there is a problem of ineffective chemotherapy to trypanosomiasis and the increasing emergence of malarial drug-resistant parasites. This research aimed to develop new dipeptide-sulfonamides as antiprotozoal agents. Background: Protozoan parasites cause severe diseases, with human African trypanosomaisis (HAT) and malaria leading the list. The noted deficiencies of existing antitrypanosomal drugs and the worldwide resurgence of malaria, accompanied by the springing up of widespread drug-resistant protozoan parasites, represent a huge challenge in infectious disease treatment in tropical regions. Methods: In order to discover new antiprotozoal agents, ten novel p-nitrobenzenesulphonamide derivatives incorporating dipeptide moiety were synthesized by the condensation reaction of 3-methyl-2-(4-nitrophenylsulphonamido)pentanoic acid (6) with substituted acetamides (4a-j) using peptide coupling reagents, characterized using 1H and 13C NMR, FTIR, HRMS, and investigated for their antimalarial and antitrypanosomal activities in vivo employing standard methods. Results: At 100 mg/kg body weight, N-(2-(2,6-dimethylphenylamino)-2-oxoethyl)-3-methyl-2-(4-nitrophenylsulfonamido)pentanamide showed the highest activity by inhibiting P. berghei parasite by 79.89%, which was comparable with the standard drug (artemether-lumefantrine 79.77%). In the antitrypanosomal study, N-(2-(4-chlorophenylamino)-2-oxoethyl)-3-methyl-2-(4-nitrophenylsulfonamido)pentanamide, N-(2-(4-fluorophenylamino)-2-oxoethyl)-3-methyl-2-(4-nitrophenylsulfonamido)pentanamide, and N-(2-(3-chlorophenylamino)-2-oxoethyl)-3-methyl-2-(4-nitrophenylsulfonamido)pentanamide were most potent in clearing Trypanosome brucei in mice. However, they were less active than the standard drug (diminazene aceturate). Molecular docking results demonstrated good binding affinity among the reported derivatives and target proteins in the active place of the protein. The outcome of haematological analysis and liver and kidney function tests showed that the new compounds had no adverse effect on the blood and organs. Conclusions: The results of this research showed that the new compounds demonstrated interesting antitrypanosomal and antimalarial potentials. However, further research should be carried out on the synthesized derivatives as promising drug candidates for trypanosomiasis and malaria.

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Antimicrobial Peptides - Small but Mighty Weapons for Plants to Fight Phytopathogens

Protein and Peptide Letters ◽

10.2174/0929866526666190619112438 ◽

2019 ◽

Vol 26 (10) ◽

pp. 720-742 ◽

Cited By ~ 8

Author(s):

Kaushik Das ◽

Karabi Datta ◽

Subhasis Karmakar ◽

Swapan K. Datta

Keyword(s):

Antimicrobial Peptides ◽

Durable Resistance ◽

Defense Responses ◽

Defense System ◽

Biotechnological Potential ◽

Functional Aspects ◽

Low Concentrations ◽

Wide Range ◽

Vital Component ◽

Pathogen Entry

Antimicrobial Peptides (AMPs) have diverse structures, varied modes of actions, and can inhibit the growth of a wide range of pathogens at low concentrations. Plants are constantly under attack by a wide range of phytopathogens causing massive yield losses worldwide. To combat these pathogens, nature has armed plants with a battery of defense responses including Antimicrobial Peptides (AMPs). These peptides form a vital component of the two-tier plant defense system. They are constitutively expressed as part of the pre-existing first line of defense against pathogen entry. When a pathogen overcomes this barrier, it faces the inducible defense system, which responds to specific molecular or effector patterns by launching an arsenal of defense responses including the production of AMPs. This review emphasizes the structural and functional aspects of different plant-derived AMPs, their homology with AMPs from other organisms, and how their biotechnological potential could generate durable resistance in a wide range of crops against different classes of phytopathogens in an environmentally friendly way without phenotypic cost.

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The Chemistry of Drugs to Treat Candida albicans

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191025153124 ◽

2019 ◽

Vol 19 (28) ◽

pp. 2554-2566 ◽

Cited By ~ 2

Author(s):

Aurelio Ortiz ◽

Estibaliz Sansinenea

Keyword(s):

Candida Species ◽

Antifungal Drugs ◽

New Drugs ◽

Drug Classes ◽

Life Threatening ◽

Antifungal Substances ◽

High Level ◽

Systemic Infections ◽

New Compounds ◽

Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

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Beehive Products as Antibacterial Agents: A Review

Antibiotics ◽

10.3390/antibiotics10060717 ◽

2021 ◽

Vol 10 (6) ◽

pp. 717

Author(s):

Rita Abou Nader ◽

Rawan Mackieh ◽

Rim Wehbe ◽

Dany El El Obeid ◽

Jean Marc Sabatier ◽

...

Keyword(s):

Antibacterial Activity ◽

Honey Bee ◽

Antibacterial Agents ◽

Royal Jelly ◽

Biological Activities ◽

Vital Role ◽

Bee Venom ◽

Bacterial Strains ◽

Wide Range ◽

Life Threatening

Honeybees are one of the most marvelous and economically beneficial insects. As pollinators, they play a vital role in every aspect of the ecosystem. Beehive products have been used for thousands of years in many cultures for the treatment of various diseases. Their healing properties have been documented in many religious texts like the Noble Quran and the Holy Bible. Honey, bee venom, propolis, pollen and royal jelly all demonstrated a richness in their bioactive compounds which make them effective against a variety of bacterial strains. Furthermore, many studies showed that honey and bee venom work as powerful antibacterial agents against a wide range of bacteria including life-threatening bacteria. Several reports documented the biological activities of honeybee products but none of them emphasized on the antibacterial activity of all beehive products. Therefore, this review aims to highlight the antibacterial activity of honey, bee venom, propolis, pollen and royal jelly, that are produced by honeybees.

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Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome

International Journal of Molecular Sciences ◽

10.3390/ijms22041617 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1617

Author(s):

Jimin Xu ◽

Judith Berastegui-Cabrera ◽

Marta Carretero-Ledesma ◽

Haiying Chen ◽

Yu Xue ◽

...

Keyword(s):

Potent Inhibitor ◽

Antiviral Drug ◽

Human Adenovirus ◽

Yield Reduction ◽

Respiratory Illnesses ◽

Molecule Inhibitor ◽

Wide Range ◽

Ic50 Values ◽

Life Threatening ◽

Salicylamide Derivatives

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.

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Recent Attempts in the Design of Efficient PVC Plasticizers with Reduced Migration

Materials ◽

10.3390/ma14040844 ◽

2021 ◽

Vol 14 (4) ◽

pp. 844

Author(s):

Joanna Czogała ◽

Ewa Pankalla ◽

Roman Turczyn

Keyword(s):

Mechanical Properties ◽

Partial Replacement ◽

Total Replacement ◽

Current Trends ◽

Poly Vinyl Chloride ◽

Wide Range ◽

Migration Resistance ◽

Secondary Plasticizer ◽

New Compounds ◽

Ethylhexyl Phthalate

This paper reviews the current trends in replacing commonly used plasticizers in poly(vinyl chloride), PVC, formulations by new compounds with reduced migration, leading to the enhancement in mechanical properties and better plasticizing efficiency. Novel plasticizers have been divided into three groups depending on the replacement strategy, i.e., total replacement, partial replacement, and internal plasticizers. Chemical and physical properties of PVC formulations containing a wide range of plasticizers have been compared, allowing observance of the improvements in polymer performance in comparison to PVC plasticized with conventionally applied bis(2-ethylhexyl) phthalate, di-n-octyl phthalate, bis(2-ethylhexyl) terephthalate and di-n-octyl terephthalate. Among a variety of newly developed plasticizers, we have indicated those presenting excellent migration resistance and advantageous mechanical properties, as well as those derived from natural sources. A separate chapter has been dedicated to the description of a synergistic effect of a mixture of two plasticizers, primary and secondary, that benefits in migration suppression when secondary plasticizer is added to PVC blend.

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Rapid Determination of Ethylene Oxide and 75 VOCs in Ambient Air with Canister Sampling and Associated Growth Issues

Separations ◽

10.3390/separations8030035 ◽

2021 ◽

Vol 8 (3) ◽

pp. 35

Author(s):

Jason Hoisington ◽

Jason S. Herrington

Keyword(s):

Ethylene Oxide ◽

Rapid Determination ◽

Complex Mixture ◽

Ambient Air ◽

Gas Chromatography Mass Spectrometry ◽

Average Accuracy ◽

Relative Standard ◽

Wide Range ◽

Us Epa

A canister-based sampling method along with preconcentrator-Gas chromatography-Mass Spectrometry (GC-MS) analysis was applied to ethylene oxide (EtO or EO) and 75 other volatile organic compounds (VOCs) in ambient air. Ambient air can contain a large variety of VOCs, and thorough analysis requires non-discriminatory sampling and a chromatographic method capable of resolving a complex mixture. Canister collection of whole air samples allows for the collection of a wide range of volatile compounds, while the simultaneous analysis of ethylene oxide and other VOCs allows for faster throughput than separate methods. The method presented is based on US EPA Method TO-15A and allows for the detection of EtO from 18 to 2500 pptv. The method has an average accuracy of 104% and precision of 13% relative standard deviation (RSD), with an instrument run time of 32 min. In addition, a link between canister cleanliness and ethylene oxide growth is observed, and potential mechanisms and cleaning strategies are addressed.

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Effects of plant extracts on antioxidant status and oxidant-induced stress in Caco-2 cells

British Journal Of Nutrition ◽

10.1017/s0007114507250469 ◽

2007 ◽

Vol 97 (2) ◽

pp. 321-328 ◽

Cited By ~ 59

Author(s):

S. Aisling Aherne ◽

Joseph P. Kerry ◽

Nora M. O'Brien

Keyword(s):

Dna Damage ◽

Plant Extract ◽

Plant Extracts ◽

Antioxidant Status ◽

Cell Injury ◽

Membrane Integrity ◽

Neutral Red ◽

Dna Integrity ◽

Cell Membrane Integrity ◽

Wide Range

Experimental evidence suggests that most herbs and spices possess a wide range of biological and pharmacological activities that may protect tissues against O2-induced damage. The objectives of the present study were: first, to determine the effects of plant extracts on the viability, membrane integrity, antioxidant status and DNA integrity of Caco-2 cells and second, to investigate the cytoprotective and genoprotective effects of these plant extracts against oxidative stress in Caco-2 cells. The plant extracts examined were rosemary (Rosmarinus officinalis L.), oregano (Origanum vulgare L.), sage (Salvia officinalis L.) and echinacea (Echinacea purpurea L.). Cell membrane integrity was assessed by the lactate dehydrogenase release assay. Viability was determined by the neutral red uptake assay (NRUA) and the concentration of compound that resulted in 50 % cell death (IC50) was calculated. Antioxidant status of the cells was assessed by measuring GSH content, catalase activity and superoxide dismutase activity. To examine their cytoprotective and genoprotective effects, Caco-2 cells were pre-treated with each plant extract for 24 h followed by exposure to H2O2. DNA damage was assessed by the comet assay and cell injury was determined by the NRUA. Rosemary was the most toxic (IC50 123 μg/ml) and echinacea the least toxic (IC50 1421 μg/ml). Sage was the only plant extract to affect the antioxidant status of the cells by increasing GSH content. Sage, oregano and rosemary protected against H2O2-induced DNA damage (olive tail moment and percentage tail DNA), whereas protection against H2O2-induced cytotoxicity was afforded by sage only.

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Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0414 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Michele Mussap ◽

Vassilios Fanos

Keyword(s):

Molecular Mechanisms ◽

Vascular Dysfunction ◽

Asymptomatic Infection ◽

Multiple Organ ◽

Therapeutic Interventions ◽

Patient Specific ◽

Wide Range ◽

Life Threatening ◽

The Individual ◽

Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

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ANTIBIOTIC SUSCEPTIBILITY PATTERN OF STAPHYLOCOCCOUS AUREUS ISOLATED FROM VARIOUS CLINICAL SPECIMENS OF TERTIARY CARE HOSPITAL IN TIRUPATI.

10.36106/ijsr/2117632 ◽

2021 ◽

pp. 14-15

Author(s):

Indira Ananthapadmanab asamy ◽

V. Pavani Sai Mounika ◽

K. Vijayakumar ◽

C.H. Srinivasa Rao

Keyword(s):

Antimicrobial Susceptibility ◽

Tertiary Care ◽

Care Hospital ◽

Susceptibility Pattern ◽

Clinical Specimens ◽

Antimicrobial Susceptibility Pattern ◽

Wide Range ◽

Life Threatening ◽

Mrsa Infection ◽

Systemic Infections

INTRODUCTION: Staphylococcus aureus causes a wide range of infections including skin and soft tissue infections to life-threatening systemic infections like sepsis, endocarditis. This study ais to evaluate the antimicrobial susceptibility pattern of S.aurues among various clinical specimens. METHODS: The study included 326 S.aurues, isolated from various clinical specimens which were subjected to antimicrobial susceptibility testing as per CLSI guidelines. RESULTS: Among the 326 isolates, the highest were from pus specimens (47.85%), and was from Orthopaedics department (28.53%). Among the isolates, 219 (67.17%) were Methicilin resistant. All isolates were sensitive to Vancomycin, and all urine isolates were sensitive to Nitrofurantoin. The highest resistance was towards Penicillin (87.42%), Erythromycin (85.28), and Ciprooxacin (83.13%). CONCLUSION: The most effective way to prevent MRSA infection in every hospital is by performing continuous surveillance of antibiotic resistance and by following an effetive antibiotic policy.

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