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1.
Int J Biol Macromol ; 273(Pt 1): 132954, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38852726

ABSTRACT

This study explores the potential of liposome encapsulated silica immobilized cytochrome P450 monooxygenase (LSICY) for bioremediation of mercury (Hg2+). Current limitations in Hg2+ reduction, including sensitivity to factors like pH and cost, necessitate alternative methods. We propose LSICY as a solution, leveraging the enzymatic activities of cytochrome P450 monooxygenase (CYPM) for Hg2+ reduction through hydroxylation and oxygenation. Our investigation employs LSICY to assess its efficacy in mitigating Hg2+ toxicity in Oryza sativa (rice) plants. Gas chromatography confirmed gibberellic acid (GA) presence in the Hg2+ reducing bacteria Priestia megaterium RP1 (PMRP1), highlighting a potential link between CYP450 activity and plant health. This study demonstrates the promise of LSICY as a sustainable and effective approach for Hg2+ bioremediation, promoting a safer soil environment.


Subject(s)
Biodegradation, Environmental , Cytochrome P-450 Enzyme System , Gibberellins , Liposomes , Mercury , Oryza , Cytochrome P-450 Enzyme System/metabolism , Gibberellins/metabolism , Gibberellins/pharmacology
2.
Bioorg Med Chem ; 27(5): 841-850, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30718062

ABSTRACT

Increasing in the alarm against the resistant bacteria due to the failure of antibiotics, thereby the need of more efficiency/potent molecule to treat infections. In the present investigation, series of piperazine derivatives 5(a-l) compounds were synthesized and they were characterised by different spectral techniques such as 1H NMR, 13C NMR, IR and LCMS. A novel copper complex (cPAmPiCaTc) was developed for the first time by using potent analog 5e and characterized by IR and LCMS. The cPAmPiCaTc evaluated for antibacterial activity and showed excellent antimicrobial effect (12 ±â€¯0.08 mm, ZOI) at MIC 20 µg/mL against MRSA compared to standard antibiotics streptomycin and bacitracin at MIC 10 µg/mL. The results show promising anti-staphylococcal action against MRSA which confirmed by membrane damage, bioelectrochemistry, gene regulation (SarA and DHFR), and in silico molecular docking studies. Further, the cPAmPiCaTc also showed excellent blood compatibility and this result pave the way for interesting metallodrug therapeutics in future against MRSA infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Coordination Complexes/pharmacology , Copper/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Piperazines/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/metabolism , Bacitracin/pharmacology , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Catalytic Domain , Coordination Complexes/chemical synthesis , Coordination Complexes/metabolism , Gene Expression Regulation/drug effects , Microbial Sensitivity Tests , Molecular Docking Simulation , Piperazines/chemical synthesis , Piperazines/metabolism , Protein Binding , Streptomycin/pharmacology , Tetrahydrofolate Dehydrogenase/chemistry , Tetrahydrofolate Dehydrogenase/genetics , Tetrahydrofolate Dehydrogenase/metabolism
3.
Microb Pathog ; 127: 106-115, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30503959

ABSTRACT

The synthesized potent piperazine analog ChDiPiCa was characterised by various spectroscopic techniques and for the first time evaluated functional membrane microdomain (FMM) disassembly in methicillin-resistant Staphylococcus aureus (MRSA). The ChDiPiCa showed excellent in vitro biocidal activity against MRSA at 26 µg/mL compared to the antibiotic streptomycin and bacitracin 14 µg/mL and 13 µg/mL at 10 µg concentration respectively. The membrane damaging property was confirmed by the SEM analysis. Further, we addressed the new approach for the first time to overcome antibiotic resistance of MRSA through membrane microdomain miss loading to lipids. By which, the ChDiPiCa confirms the significant activity in miss loading of FMM of MRSA which is validated by the fatty acid profile and lipid analysis. The result shows that, altered saturated (Lauric acid and Myristic acid), mono unsaturated (Oleic acid), and poly unsaturated (Linoleic acid and Linolenic acid) fatty acids and hypothesises, altered the membrane functional lipids. For the better understanding of miss loading of FMM by the ChDiPiCa, the in-silico molecular docking studies was analyzed and confirmed the predicted role. This suggests the way to develop ChDiPiCa in medicinal chemistry as anti-MRSA candidates and also this report opens up new window to treat microbial pathogens and infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Membrane Microdomains/drug effects , Membrane Microdomains/metabolism , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/metabolism , Piperazine/pharmacology , Anti-Bacterial Agents/chemical synthesis , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Lipid Metabolism/drug effects , Methicillin-Resistant Staphylococcus aureus/ultrastructure , Microscopy, Electron, Scanning , Molecular Docking Simulation , Piperazine/analogs & derivatives , Piperazine/chemical synthesis
4.
Microb Pathog ; 123: 275-284, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30041001

ABSTRACT

Bacterial adhesion is a threshold event in the formation of biofilms which leads to serious bacterial diseases. This shows that the underlining the problem is interesting and need to solve the problem of biofilm-related complications. To support this, in the present study, we first time initiated to understand the role of methicillin-resistant Staphylococcus aureus (MRSA) biofilm using previously developed benzodioxane midst piperazine decorated chitosan silver nanoparticles (BP*C@AgNPs). The BP*C@AgNPs studied for antimicrobial, anti-biofilm, biofilm adherence inhibition, the role of ions in biofilm, and an antibiotic cocktail in the treatment of biofilm was assessed. The results showed that, the significant biocidal role of BP*C@AgNPs in controlling the MRSA biofilm and interaction of biofilm protein to calcium ions were significantly decreased. This confirms that calcium ion involved in the biofilm formation and for the treatment of BP*C@AgNPs, cocktail of enzyme and antibiotic have the promising therapeutic value was observed. In future the locking of biofilm protein and its expression in presence of calcium ion was interesting, and greater application related to biofilm infection was warrantable.


Subject(s)
Biofilms/drug effects , Metal Nanoparticles/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Silver/pharmacology , Amino Acid Sequence , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Bacterial Adhesion/drug effects , Benzodioxoles , Binding Sites , Calcium/metabolism , Chitosan , Drug Combinations , Endopeptidase K/pharmacology , Heterocyclic Compounds, 2-Ring/chemistry , Heterocyclic Compounds, 2-Ring/pharmacology , Microbial Sensitivity Tests , Staphylococcal Infections/microbiology , Virulence/drug effects
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