Synthesis, Characterization and Biological Activity of ONO Donor Schiff Base and its Metal Complexes

A new Schiff base ligand (E)-2-((7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)-N-(5- methyl-3-phenyl-1H-indol-2-yl)hydrazine carboxamide (L) (3) was synthesized by the reaction of N-(5-methyl-3-phenyl-1H-indol-2-yl)hydrazinecarboxamide (1) and 7-hydroxy-4-methyl-2-oxo-2Hchromene- 8-carbaldehyde (2). The Cu(II), Co(II), Ni(II) and Zn(II) metal complexes (4a-d) were synthesized and its structural elucidation was done by different spectral techniques. The Schiff base (3) behaves as ONO donor ligand and forms the complexes of the sort [M(L)(Cl)(H2O)2] for Cu(II) (4a) and Zn(II) (4d) and [M(L)2] for Co(II) (4b) and Ni(II) (4c). Compounds (3) and (4a-d) were tested in vitro for antimicrobial action, cytotoxicity property against Artemia salina and anti-tuberculosis assay against Mycobacterium tuberculosis (ATCC 25177). The metal complexes showed very good biological activity.

Exploration of the antimicrobial synergy between selected natural substances on Streptococcus mutans to identify candidates for the control of dental caries

Dental caries is caused by dental plaque, a community of micro-organisms embedded in an extracellular polymer matrix as a biofilm on the tooth surface. Natural products that are widely available could be used as an alternative or adjunctive anti-caries therapy. Sometimes, when two products are used together, they yield a more powerful antimicrobial effect than the anticipated additive effect. These synergistic combinations are often better treatment options because individual agents may not have sufficient antimicrobial action to be effective when used alone. Cranberries contain phenolic compounds like proanthocyanidins (PAC) that disrupt biofilm formation. Manuka honey has high concentrations of the agent methylglyoxal, which is cariostatic. Because these agents have varied modes of antimicrobial action, they show potential for possible synergistic effects when paired. Various cranberry extracts were tested pairwise with manuka honey or methylglyoxal by well-diffusion assays and 96-well checkerboard assays in the presence of Streptococcus mutans to test for synergy. Synergy was demonstrated in two of the cranberry extracts paired with manuka honey. The synergistic combinations found in this research thus can be considered as candidates for the formulation of a dentifrice that could be used to inhibit the formation of dental plaque and thereby avoid the development of caries.

A Systematic Review on Nanoencapsulation Natural Antimicrobials in Foods: In Vitro versus In Situ Evaluation, Mechanisms of Action and Implications on Physical-Chemical Quality

Natural antimicrobials (NA) have stood out in the last decade due to the growing demand for reducing chemical preservatives in food. Once solubility, stability, and changes in sensory attributes could limit their applications in foods, several studies were published suggesting micro-/nanoencapsulation to overcome such challenges. Thus, for our systematic review the Science Direct, Web of Science, Scopus, and Pub Med databases were chosen to recover papers published from 2010 to 2020. After reviewing all titles/abstracts and keywords for the full-text papers, key data were extracted and synthesized. The systematic review proposed to compare the antimicrobial efficacy between nanoencapsulated NA (nNA) and its free form in vitro and in situ studies, since although in vitro studies are often used in studies, they present characteristics and properties that are different from those found in foods; providing a comprehensive understanding of primary mechanisms of action of the nNA in foods; and analyzing the effects on quality parameters of foods. Essential oils and nanoemulsions (10.9–100 nm) have received significant attention and showed higher antimicrobial efficacy without sensory impairments compared to free NA. Regarding nNA mechanisms: (i) nanoencapsulation provides a slow-prolonged release to promote antimicrobial action over time, and (ii) prevents interactions with food constituents that in turn impair antimicrobial action. Besides in vitro antifungal and antibacterial, nNA also demonstrated antioxidant activity—potential to shelf life extension in food. However, of the studies involving nanoencapsulated natural antimicrobials used in this review, little attention was placed on proximate composition, sensory, and rheological evaluation. We encourage further in situ studies once data differ from in vitro assay, suggesting food matrix greatly influences NA mechanisms.

On the effectiveness of new organophosphates in the treatment of diphtheria

In recent years, there have been reports of the antimicrobial action of some organic phosphorus compounds from the group of phosphinic acid derivatives (Dok and Fridman, 1952; S. M. Vyaseleva et al., 1960).

Evaluation of Host Defense Peptide (CaD23)-Antibiotic Interaction and Mechanism of Action: Insights From Experimental and Molecular Dynamics Simulations Studies

Background/Aim: Host defense peptides (HDPs) have the potential to provide a novel solution to antimicrobial resistance (AMR) in view of their unique and broad-spectrum antimicrobial activities. We had recently developed a novel hybrid HDP based on LL-37 and human beta-defensin-2, named CaD23, which was shown to exhibit good in vivo antimicrobial efficacy against Staphylococcus aureus in a bacterial keratitis murine model. This study aimed to examine the potential CaD23-antibiotic synergism and the secondary structure and underlying mechanism of action of CaD23.Methods: Peptide-antibiotic interaction was evaluated against S. aureus, methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa using established checkerboard and time-kill assays. Fractional inhibitory concentration index (FICI) was calculated and interpreted as synergistic (FIC<0.5), additive (FIC between 0.5–1.0), indifferent (FIC between >1.0 and ≤4), or antagonistic (FIC>4). SYTOX green uptake assay was performed to determine the membrane-permeabilising action of CaD23. Molecular dynamics (MD) simulations were performed to evaluate the interaction of CaD23 with bacterial and mammalian mimetic membranes. Circular dichroism (CD) spectroscopy was also performed to examine the secondary structures of CaD23.Results: CaD23-amikacin and CaD23-levofloxacin combination treatment exhibited a strong additive effect against S. aureus SH1000 (FICI = 0.60–0.69) and MRSA43300 (FICI = 0.56–0.60) but an indifferent effect against P. aeruginosa (FIC = 1.03–1.15). CaD23 (at 25 μg/ml; 2xMIC) completely killed S. aureus within 30 min. When used at sub-MIC concentration (3.1 μg/ml; 0.25xMIC), it was able to expedite the antimicrobial action of amikacin against S. aureus by 50%. The rapid antimicrobial action of CaD23 was attributed to the underlying membrane-permeabilising mechanism of action, evidenced by the SYTOX green uptake assay and MD simulations studies. MD simulations revealed that cationicity, alpha-helicity, amphiphilicity and hydrophobicity (related to the Trp residue at C-terminal) play important roles in the antimicrobial action of CaD23. The secondary structures of CaD23 observed in MD simulations were validated by CD spectroscopy.Conclusion: CaD23 is a novel alpha-helical, membrane-active synthetic HDP that can enhance and expedite the antimicrobial action of antibiotics against Gram-positive bacteria when used in combination. MD simulations serves as a powerful tool in revealing the peptide secondary structure, dissecting the mechanism of action, and guiding the design and optimisation of HDPs.