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1.
Int J Mol Sci ; 22(11)2021 May 31.
Article in English | MEDLINE | ID: mdl-34072929

ABSTRACT

Metalloid tellurium is characterized as a chemical element belonging to the chalcogen group without known biological function. However, its compounds, especially the oxyanions, exert numerous negative effects on both prokaryotic and eukaryotic organisms. Recent evidence suggests that increasing environmental pollution with tellurium has a causal link to autoimmune, neurodegenerative and oncological diseases. In this review, we provide an overview about the current knowledge on the mechanisms of tellurium compounds' toxicity in bacteria and humans and we summarise the various ways organisms cope and detoxify these compounds. Over the last decades, several gene clusters conferring resistance to tellurium compounds have been identified in a variety of bacterial species and strains. These genetic determinants exhibit great genetic and functional diversity. Besides the existence of specific resistance mechanisms, tellurium and its toxic compounds interact with molecular systems, mediating general detoxification and mitigation of oxidative stress. We also discuss the similarity of tellurium and selenium biochemistry and the impact of their compounds on humans.


Subject(s)
Eukaryotic Cells/drug effects , Oxidative Stress/drug effects , Prokaryotic Cells/drug effects , Tellurium/adverse effects , Anions/adverse effects , Bacteria/drug effects , Environmental Pollution/analysis , Humans , Selenium/chemistry , Tellurium/chemistry , Tellurium/toxicity
2.
J Biomol Struct Dyn ; 37(16): 4222-4237, 2019 10.
Article in English | MEDLINE | ID: mdl-30526389

ABSTRACT

Emerging widespread bacterial resistance to current antibiotics with traditional targets is one of the major global concerns. Therefore, so many investigations are exploring the potential of other druggable macromolecules of bacteria such as replication machinery components that are not addressed by previous antibiotics. DNA polymerase is the major part of this machine. However, a few studies have been done on it so far. In this respect, we report the discovery of four new plant-based leads against DNA polymerase (pol) IIIC (three leads) and pol IIIE (one lead) of Gram-positive and negative bacteria by combining a sequentially constrained high-throughput virtual screenings on Traditional Chinese Medicine Database with in vitro assays. The compounds displayed relatively good levels of inhibitory effect. They were active against their designated targets at micromolar concentrations. The IC50 values for them are ranged from 25 to 111 µM. In addition, they showed minimum inhibitory concentrations in the range of 8-128 µg/mL against five representatives of pathogenic bacteria species. However, they were inactive against Pseudomonas aeruginosa. Given these results, these leads hold promise for future modification and optimization to be more effective in lower concentrations and also against most of the important bacterial species. Communicated by Ramaswamy H. Sarma.


Subject(s)
DNA Polymerase III/chemistry , DNA Replication/drug effects , Lead/pharmacology , Nucleic Acid Synthesis Inhibitors/pharmacology , Anti-Bacterial Agents/adverse effects , Computer Simulation , DNA Polymerase III/antagonists & inhibitors , Drug Resistance, Bacterial/genetics , Escherichia coli/drug effects , Escherichia coli/pathogenicity , Humans , Lead/chemistry , Microbial Sensitivity Tests , Nucleic Acid Synthesis Inhibitors/chemistry , Prokaryotic Cells/drug effects , Prokaryotic Cells/microbiology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity
3.
Nanotoxicology ; 11(9-10): 1102-1114, 2017.
Article in English | MEDLINE | ID: mdl-29119849

ABSTRACT

Graphene oxide (GO)-based materials are increasingly being used in medical materials and consumer products. However, their sublethal effects on biological systems are poorly understood. Here, we report that GO (at 10 to 160 mg/L) induced significant inhibitory effects on the growth of different unicellular organisms, including eukaryotes (i.e. Saccharomyces cerevisiae, Candida albicans, and Komagataella pastoris) and prokaryotes (Pseudomonas fluorescens). Growth inhibition could not be explained by commonly reported cytotoxicity mechanisms such as plasma membrane damage or oxidative stress. Based on transcriptomic analysis and measurement of extra- and intracellular iron concentrations, we show that the inhibitory effect of GO was mainly attributable to iron deficiency caused by binding to the O-functional groups of GO, which sequestered iron and disrupted iron-related physiological and metabolic processes. This inhibitory mechanism was corroborated with supplementary experiments, where adding bathophenanthroline disulfonate-an iron chelating agent-to the culture medium exerted similar inhibition, whereas removing surface O-functional groups of GO decreased iron sequestration and significantly alleviated the inhibitory effect. These findings highlight a potential indirect detrimental effect of nanomaterials (i.e. scavenging of critical nutrients), and encourage research on potential biomedical applications of GO-based materials to sequester iron and enhance treatment of iron-dependent diseases such as cancer and some pathogenic infections.


Subject(s)
Cell Proliferation/drug effects , Graphite/toxicity , Iron/metabolism , Nanostructures/toxicity , Cell Cycle/drug effects , Cell Membrane/drug effects , Dose-Response Relationship, Drug , Eukaryotic Cells/drug effects , Eukaryotic Cells/metabolism , Graphite/chemistry , Humans , Nanostructures/chemistry , Oxidative Stress/drug effects , Oxides , Prokaryotic Cells/drug effects , Prokaryotic Cells/metabolism
4.
J Ethnopharmacol ; 111(3): 592-7, 2007 May 22.
Article in English | MEDLINE | ID: mdl-17321090

ABSTRACT

Through data mining a historic herbal text, we identified Atuna racemosa-Raf. as a plant with alleged antibacterial properties. We have shown that these purported antibacterial properties are most prominent in the kernel of the nut of the plant. While working with traditional healers in Samoa during a botanical collection trip, we identified a range of maturity stages of the kernel. Here we show that the antibacterial properties are different at different stages of kernel maturity, and that the immature kernels have a lower minimal inhibitory concentration (MIC) than the mature kernels. Additionally, we show there is a negative correlation between the antibacterial properties and cytotoxic properties (a stronger antibiotic is less cytotoxic), suggesting there are two separate compounds with disparate characteristics. These findings have implications for the use of this natural product as an antibiotic and chemotherapeutic agent.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Plant Extracts/pharmacology , Rosaceae , Seeds/growth & development , Anti-Bacterial Agents/administration & dosage , Antineoplastic Agents/administration & dosage , Cell Cycle/drug effects , Cell Death/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Eukaryotic Cells/drug effects , Humans , Jurkat Cells , Medicine, Traditional , Microbial Sensitivity Tests , Plant Extracts/administration & dosage , Plants, Medicinal , Prokaryotic Cells/drug effects , Rosaceae/growth & development , Samoa
5.
J Oleo Sci ; 56(1): 43-7, 2006.
Article in English | MEDLINE | ID: mdl-17693698

ABSTRACT

We isolated the glycolipids fraction from spinach (Spinacia oleracea L.) and found that the fraction inhibited the activities of prokaryotic DNA polymerase I from Escherichia coli (E. coli) and cell growth of E. coli. The fraction contained mainly three glycolipids, monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG), and purified SQDG inhibited these activities, however, purified MGDG and DGDG had no influence. In the tested strains of E. coli, SQDG inhibited the cell proliferation of the JM109 strain. It could be considered that a SQDG-containing thylakoid membrane in plant chloroplasts might have anti-bacterial activity.


Subject(s)
Cell Proliferation/drug effects , DNA Polymerase I/antagonists & inhibitors , Escherichia coli/cytology , Escherichia coli/enzymology , Glycolipids/pharmacology , Growth Inhibitors/pharmacology , DNA Polymerase I/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Escherichia coli/drug effects , Glycolipids/chemistry , Glycolipids/isolation & purification , Growth Inhibitors/chemistry , Growth Inhibitors/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Prokaryotic Cells/drug effects , Prokaryotic Cells/enzymology , Spinacia oleracea
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