Chemical and Biological Properties and Mode of Action of 8-Carbamoyl-3-(2-Chloroethyl)Imidazo [5,1-d]-1,2,3,5-Tetrazin-4(3H)-One, A Novel Broad Spectrum Antitumour Agent

Antimicrobial peptides are an attractive alternative to traditional antibiotics, due to their physicochemical properties, activity toward a broad spectrum of bacteria, and mode-of-actions distinct from those used by current antibiotics. In general, antimicrobial peptides kill bacteria by either disrupting their membrane, or by entering inside bacterial cells to interact with intracellular components. Characterization of their mode-of-action is essential to improve their activity, avoid resistance in bacterial pathogens, and accelerate their use as therapeutics. Here we review experimental biophysical tools that can be employed with model membranes and bacterial cells to characterize the mode-of-action of antimicrobial peptides.

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Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1518034113 ◽

2016 ◽

Vol 113 (6) ◽

pp. 1630-1635 ◽

Cited By ~ 40

Author(s):

Maxwell Z. Wilson ◽

Rurun Wang ◽

Zemer Gitai ◽

Mohammad R. Seyedsayamdost

Keyword(s):

Broad Spectrum ◽

Marine Bacteria ◽

Anticancer Agents ◽

Mode Of Action ◽

Resistance Mechanism ◽

Acid Resistance ◽

Structural Features ◽

Anticancer Activities ◽

Tropodithietic Acid ◽

Biochemical Analyses

While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal–bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA’s cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed.

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Mode of Action and Biological Properties of Insoluble Interferon

Experimental Biology and Medicine ◽

10.3181/00379727-147-38329 ◽

1974 ◽

Vol 147 (1) ◽

pp. 293-299 ◽

Cited By ~ 15

Author(s):

C. Chany ◽

H. Ankel ◽

B. Galliot ◽

M. J. Chevalier ◽

A. Gregoire

Keyword(s):

Mode Of Action ◽

Biological Properties

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The Potential of RIP (Ribosome Inactivating Protein) as Biopesticides

Buletin Eboni ◽

10.20886/buleboni.5271 ◽

2019 ◽

Vol 1 (1) ◽

pp. 33-39

Author(s):

Tati Suharti ◽

Dharmawati F Djam’an

Keyword(s):

Protein Synthesis ◽

Broad Spectrum ◽

Plant Pathogen ◽

Mode Of Action ◽

Castor Bean ◽

Insect Pests ◽

Bitter Melon ◽

Ribosome Inactivating Protein ◽

High Potency ◽

Anti Fungal

RIP (Ribosome Inactivating Protein) produced by plants that can act as a plant defense from pest and disease. This protein is widely used as an anti-fungal, anti-bacterial, anti-virus and anti-insect. Therefore, RIP contained in plants has the potential to be used for environmentally friendly biopesticides. The purpose of this paper is to provide information on RIP derived from plants and its potential as a biopesticide.The mode of action of RIP works is by inhibiting protein synthesis during translating process of pest and plant pathogen. RIP has a broad spectrum so that it can overcome insect pests from various orders and pathogens both fungi, bacteria and viruses. Some types of plants that contain RIP include neem, ginger, turmeric, galangal, castor bean, jatropha, soursop and bitter melon. RP applications can be in the form of oil, essential oils, solutions, flour, ash and simplicia. RIP can be applied to seeds, seeds, plants and post-harvest products. The advantages of using RIP include easily available materials, inexpensive, easy to application and environmentally friendly.The plants contain RP has high potency to commercially developed so in the future, the controlling of pest and disease rely on the plants contain RIP both direct and in the pesticides formulations form. Therefore echo friendly plantation programme can be realized.

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