Schiff bases derived from 4-amino-N-substituted benzenesulfonamide: synthesis, spectral characterisation and MIC evaluation

ABSTRACT. The present study is aimed to synthesise Schiff bases from sulfathiazole/ sulfamethoxazole/ sulfadimidine with 2-hydroxybenzaldehyde. The synthesized Schiff bases were characterized by analytical data, IR, 1H-NMR, 13C-NMR, UV-Vis spectra, mass spectra and screened for antibacterial activity against gram positive bacteria Staphylococcus aureus and gram negative bacteria Salmonella typhiand antifungal activity against Candida albicans and Mucor by disc diffusion method. Zone of inhibition indicated that the Schiff base possessed highly potent antimicrobial activity when compared to sulpha drugs.                     KEY WORDS: 4-Amino-N-(1,3-thiazol-2-yl)benzenesulfonamide, 4-amino-N-(5-methylisoxazol-3-yl)-benzenesulfonamide, 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide, 2-hydroxybenzaldehyde, antimicrobial activity   Bull. Chem. Soc. Ethiop. 2021, 35(2), 435-448.  DOI: https://dx.doi.org/10.4314/bcse.v35i2.1

Bound To Shock: Protection from Lethal Endotoxemic Shock by a Novel, Nontoxic, Alkylpolyamine Lipopolysaccharide Sequestrant

Lipopolysaccharide (LPS), or endotoxin, a structural component of gram-negative bacterial outer membranes, plays a key role in the pathogenesis of septic shock, a syndrome of severe systemic inflammation which leads to multiple-system organ failure. Despite advances in antimicrobial chemotherapy, sepsis continues to be the commonest cause of death in the critically ill patient. This is attributable to the lack of therapeutic options that aim at limiting the exposure to the toxin and the prevention of subsequent downstream inflammatory processes. Polymyxin B (PMB), a peptide antibiotic, is a prototype small molecule that binds and neutralizes LPS toxicity. However, the antibiotic is too toxic for systemic use as an LPS sequestrant. Based on a nuclear magnetic resonance-derived model of polymyxin B-LPS complex, we had earlier identified the pharmacophore necessary for optimal recognition and neutralization of the toxin. Iterative cycles of pharmacophore-based ligand design and evaluation have yielded a synthetically easily accessible N1,mono-alkyl-mono-homologated spermine derivative, DS-96. We have found that DS-96 binds LPS and neutralizes its toxicity with a potency indistinguishable from that of PMB in a wide range of in vitro assays, affords complete protection in a murine model of LPS-induced lethality, and is apparently nontoxic in vertebrate animal models.This work was supported by NIH grant 1R01 AI50107

Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides

Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible correlation of these with the in vivo onset of activity have only recently been proposed. In addition, such thresholds observed in model membranes occur at local peptide concentrations close to full membrane coverage. In this work we fully develop an interaction model of antimicrobial peptides with biological membranes; by exploring the consequences of the underlying partition formalism we arrive at a relationship that provides antibacterial activity prediction from two biophysical parameters: the affinity of the peptide to the membrane and the critical bound peptide to lipid ratio. A straightforward and robust method to implement this relationship, with potential application to high-throughput screening approaches, is presented and tested. In addition, disruptive thresholds in model membranes and the onset of antibacterial peptide activity are shown to occur over the same range of locally bound peptide concentrations (10 to 100 mM), which conciliates the two types of observations

The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production

Abstract Innate defense mechanisms are aimed at quickly containing and removing infectious microorganisms and involve local stromal and immune cell activation, neutrophil recruitment and activation and the induction of host defense peptides (defensins and cathelicidins), acute phase proteins and complement activation. As an alternative to antibiotics, innate immune mechanisms are highly relevant as they offer rapid general ways to, at least partially, protect against infections and enable the build-up of a sufficient adaptive immune response. This review describes two classes of promising alternatives to antibiotics based on components of the innate host defense. First we describe immunoglobulins applied to mimic the way in which they work in the newborn as locally acting broadly active defense molecules enforcing innate immunity barriers. Secondly, the potential of host defense peptides with different modes of action, used directly, induced in situ or used as vaccine adjuvants is described

Mixed ligand complexes of nickel(II) with imidazoles and some dipeptides

468-471The computer based analysis of the pH titration data in the Ni(II)-imidazole (him)/histamine (hist)/L-histidine(his) (A)glycyl-L-phenylalanine(glyphe), glycyl-L-tyrosine(glytyr) and L-tyrosylglycine (tyrgly) (B) systems shows the presence of NiAB, NiABH-1, NiA2B or NiAB2 mixed ligand species. The results demonstrate that him, hist and his(A) are respectively mono-, bi- and tri-dentate and the dipeptide(B) ligands are bidentate in NiAB, NiA2B and NiAB2 complexes. The amide deprotonated dipeptide (BH-1) appears to bind in a tridentate mode in the NiABH-1 species in the him(A) systems, while the trends in results clearly demonstrate the bidentate binding of (BH-1) in the hist/his(A) mixed ligand systems. &nbsp