β-Lactone natural products and derivatives inactivate homoserine transacetylase, a target for antimicrobial agents

Introduction: Natural products are the source of a large fraction of the current pharmaceutics available against human disease. However, the discovery of novel compounds with new mechanisms of action is becoming increasingly challenging. We focused our work on soil-dwelling Myxobacteria from highly diverse samples, which are more and more recognized as an important natural product source. Methodology: Our discovery pipeline combines traditional whole cell-based activity screens with state-of-the-art analytical techniques and a comprehensive dereplication process. Having identified an antimicrobial compound we aim at elucidating its target, MOA and MOR in diverse microbiological screens and by applying ‘omic’ technologies. Results: Two case studies of currently investigated compound classes will be highlighted. Cystobactamids are novel topoisomerase inhibitors that display very pronounced activity on Gram-positive and Gram-negative bacteria. Telomycins from Streptomyces canus bind to cardiolipin and our studies revealed other putative cellular targets. Conclusion: We were able to isolate several new natural products with potent and selective activity against clinically relevant pathogens. Interestingly, underlying MOAs often differ from those of already described antimicrobial agents.

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Natural products as antimicrobial agents

Food Control ◽

10.1016/j.foodcont.2014.05.047 ◽

2014 ◽

Vol 46 ◽

pp. 412-429 ◽

Cited By ~ 415

Author(s):

Rabin Gyawali ◽

Salam A. Ibrahim

Keyword(s):

Natural Products ◽

Antimicrobial Agents

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Screening of natural products for antimicrobial agents

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/bf01964283 ◽

1990 ◽

Vol 9 (7) ◽

pp. 455-461 ◽

Cited By ~ 57

Author(s):

L. Silver ◽

K. Bostian

Keyword(s):

Natural Products ◽

Antimicrobial Agents

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Comparative Evaluation of the Inhibitory Potential of Synthetic N-Heterocycles, Cu/Fe3O4@SiO2 Nanocomposites and Some Natural Products against Non-Resistant and Antibiotic-Resistant Acinetobacter baumannii

Pharmaceutical Sciences ◽

10.34172/ps.2020.12 ◽

2020 ◽

Vol 26 (2) ◽

pp. 184-192

Author(s):

Jalal Mardaneh ◽

Hamid Beyzaei ◽

Seyed Hadi Hashemi ◽

Behzad Ghasemi ◽

Abbas Rahdar

Keyword(s):

Natural Products ◽

Acinetobacter Baumannii ◽

Green Tea ◽

Antimicrobial Agents ◽

Curcuma Longa ◽

Tea Catechins ◽

Green Tea Catechins ◽

Trachyspermum Ammi ◽

Heterocyclic Derivatives ◽

Sio2 Nanocomposites

Background: Acinetobacter baumannii is a common infectious agent in hospitals. New antimicrobial agents are identified and prepared to combat these bacterial pathogens. In this context, the blocking potentials of a series of synthesized N-heterocyclic compounds, Cu/Fe3O4@SiO2 nanocomposites, glycine, poly-L-lysine, nisin and hydroalcoholic extracts of Trachyspermum ammi, Curcuma longa and green tea catechins were evaluated against non-resistant and multidrug-resistant strains of A. baumannii. Methods: Solutions of heterocyclic derivatives and hydroalcoholic extracts of Trachyspermum ammi, Curcuma longa and green tea catechins were prepared at initial concentration of 10240 μg ml-1 in 10% DMSO. Other compounds were dissolved in water at the same concentrations. Their in vitro inhibitory activity was assessed by determination of IZD, MIC and MBC values. Results: Glycine, poly-L-lysine, nisin, Curcuma longa and green tea catechins extracts, and thiazoles 3a, 3d and 3f were ineffective at their initial concentrations. Heterocyclic derivatives 7a-f, 3c, 3e and 3h, Cu/Fe3O4@SiO2 nanocomposites and Trachyspermum ammi extract could block the growth of bacterial strains with IZDs (7.40-15.51 mm), MICs (32-1024 µg ml-1) and MBCs (128-2048 µg ml-1). Conclusion: Among synthetic chemicals and natural products, the best antimicrobial effects were recorded with (E)-2-(5-acetyl-4-methylthiazol-2-yl)-2-(thiazolidin-2-ylidene)acetonitrile (7b) and the extract of Trachyspermum ammi. It is imperative that their toxic and histopathologic effects were assessed in future researches. It is predicted that the essential oil of Trachyspermum ammi will improve its antibacterial activities.

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New Insights into and Updates on Antimicrobial Agents from Natural Products

BioMed Research International ◽

10.1155/2019/7079864 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Taoufik Ghrairi ◽

Sophie Jaraud ◽

Artur Alves ◽

Yannick Fleury ◽

Allaeddin El Salabi ◽

...

Keyword(s):

Natural Products ◽

Antimicrobial Agents

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Plant Derived Natural Products against Pseudomonas aeruginosa and Staphylococcus aureus: Antibiofilm Activity and Molecular Mechanisms

Molecules ◽

10.3390/molecules25215024 ◽

2020 ◽

Vol 25 (21) ◽

pp. 5024

Author(s):

Francesca Guzzo ◽

Monica Scognamiglio ◽

Antonio Fiorentino ◽

Elisabetta Buommino ◽

Brigida D’Abrosca

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Natural Products ◽

Molecular Mechanisms ◽

Antimicrobial Agents ◽

Antibiofilm Activity ◽

Complex Structures ◽

Skin Infections ◽

Human Pathogens ◽

And Staphylococcus Aureus

Bacteria are social organisms able to build complex structures, such as biofilms, that are highly organized surface-associated communities of microorganisms, encased within a self- produced extracellular matrix. Biofilm is commonly associated with many health problems since its formation increases resistance to antibiotics and antimicrobial agents, as in the case of Pseudomonas aeruginosa and Staphylococcus aureus, two human pathogens causing major concern. P. aeruginosa is responsible for severe nosocomial infections, the most frequent of which is ventilator-associated pneumonia, while S. aureus causes several problems, like skin infections, septic arthritis, and endocarditis, to name just a few. Literature data suggest that natural products from plants, bacteria, fungi, and marine organisms have proven to be effective as anti-biofilm agents, inhibiting the formation of the polymer matrix, suppressing cell adhesion and attachment, and decreasing the virulence factors’ production, thereby blocking the quorum sensing network. Here, we focus on plant derived chemicals, and provide an updated literature review on the anti-biofilm properties of terpenes, flavonoids, alkaloids, and phenolic compounds. Moreover, whenever information is available, we also report the mechanisms of action.

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The Antimicrobial Activity of Cannabinoids

Antibiotics ◽

10.3390/antibiotics9070406 ◽

2020 ◽

Vol 9 (7) ◽

pp. 406

Author(s):

John A. Karas ◽

Labell J. M. Wong ◽

Olivia K. A. Paulin ◽

Amna C. Mazeh ◽

Maytham H. Hussein ◽

...

Keyword(s):

Antimicrobial Activity ◽

Natural Products ◽

Antimicrobial Agents ◽

Cannabis Sativa ◽

Antimicrobial Properties ◽

Herbaceous Plant ◽

Structure Activity Relationships ◽

Modes Of Action ◽

Structure Activity ◽

Rapid Emergence

A post-antibiotic world is fast becoming a reality, given the rapid emergence of pathogens that are resistant to current drugs. Therefore, there is an urgent need to discover new classes of potent antimicrobial agents with novel modes of action. Cannabis sativa is an herbaceous plant that has been used for millennia for medicinal and recreational purposes. Its bioactivity is largely due to a class of compounds known as cannabinoids. Recently, these natural products and their analogs have been screened for their antimicrobial properties, in the quest to discover new anti-infective agents. This paper seeks to review the research to date on cannabinoids in this context, including an analysis of structure–activity relationships. It is hoped that it will stimulate further interest in this important issue.

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The Fungal Metabolites with Potential Antiplasmodial Activity

Current Medicinal Chemistry ◽

10.2174/0929867325666180313105406 ◽

2018 ◽

Vol 25 (31) ◽

pp. 3796-3825 ◽

Cited By ~ 1

Author(s):

Bin Yang ◽

Jingxia Huang ◽

Xuefeng Zhou ◽

Xiuping Lin ◽

Juan Liu ◽

...

Keyword(s):

Natural Products ◽

Antimicrobial Agents ◽

Antimalarial Activity ◽

Management Strategies ◽

Marine Fungus ◽

Chemical Diversity ◽

Biologically Active ◽

Antiplasmodial Activity ◽

Marine Environments ◽

Tropical Regions

Malaria caused by Plasmodium parasites is amongst many prevalent public health concerns in several tropical regions of the world. Nowadays, the parasite resistance patterns to most currently used drugs in therapy and insecticides have created an urgent need for new chemical entities exhibiting new modes of action and management strategies. Fungus has been proven to be an excellent source of biologically active compounds, which have been screened for antiplasmodial activity as potential sources of new antimalarial drugs. This review summarizes the current 255 natural products from fungus, which may possess antimalarial activity and can be classified as sesquiterpenes, diterpenes, sesterterpenes, alkaloids, peptides depsipeptides, xanthones, anthraquinones, anthrones, bioxanthracenes, bixanthones, preussomerins, depsidones, phenols, trichothecenes, azaphliones, macrolides, and steroids. However, the treatments available for malaria are limited. Thus, the identification of novel antimicrobial agents should be continued, and all possible strategies should be explored. Carrying forward the antimalarial screening in exited terrestrial and marine natural products library, and finding the new natural products in new resources, particularly those living in marine environments, are still important approaches to find new antimalarial agents. Unusual marine environments are associated with chemical diversity, leading to a resource of novel active substances for the development of bioactive products. Finding new antimalarial natural products in marine fungus, particularly those living in deep-sea and special marine environments, is an important approach to identify novel active agents.

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