Confronting the Threat: Designing Highly Effective bis-Benzimidazolium Agents to Overcome Biofilm Persistence and Antimicrobial Resistance.

The objective of this study is to take the initial steps toward developing novel antibiotics to counteract the escalating problem of antimicrobial and bacterial persistence, particularly in relation to biofilms. Our approach involves emulating the structural characteristics of cationic antimicrobial peptides. To circumvent resistance development, we have designed a library of bis-benzimidazolium salts that selectively target the microbial membranes in a nonspecific manner.

Highly Active, Entirely Biobased Antimicrobial Pickering Emulsions.

We present the development of surfactant-free, silica-free and fully biobased oil-in-water antimicrobial Pickering emulsions, based on the self-assembly of β-cyclodextrin and phytoantimicrobial oils (terpinen-4-ol or carvacrol). Undecylenic acid (UA), derived from castor oil, can be used as bio-based drug to treat fungal infection, but is less effective than petroleum-based drugs as azole derivatives. To maximize its antifungal potential, we have incorporated UA in fully biobased Pickering emulsions.

Phytochemical- and Cyclodextrin-Based Pickering Emulsions: Natural Potentiators of Antibacterial, Antifungal, and Antibiofilm Activity.

We present self-assembled Pickering emulsions containing biocidal phytochemical oils (carvacrol and terpinen-4-ol) and β-cyclodextrin able to potentiate the antimicrobial and antibiofilm activity of miconazoctylium bromide. The carvacrol-containing emulsion is 2-fold more sensitive against and and highly active against , compared to the commercial cream containing miconazole nitrate. Moreover, this emulsion shows a synergistic effect against fungi, additive responses against bacteria, and remarkable staphylococcal biofilm eradication.

Benzimidazolium salts prevent and disrupt methicillin-resistant biofilms.

Emergence of resistant bacteria encourages us to develop new antibiotics and strategies to compensate for the different mechanisms of resistance they acquire. One of the defense mechanisms of resistant bacteria is the formation of biofilms. Herein we show that benzimidazolium salts with various flexible or rigid side chains act as strong antibiotic and antibiofilm agents.

Antimicrobial and Antibiofilm Activity of Disubstituted Bis-benzimidazolium Salts.

The increased prevalence of antibiotic-resistant bacteria is a critical issue for human health. Developing new antibiotic agents is vital for fighting persistent infections and lowering mortality rates. In this study, we designed lutidine-disubstituted bis-benzimidazolium salts (lutidine-bis-benzimidazolium core with octyl, adamantyl, and cholesteryl lipophilic side chains), and tested their antimicrobial activity, their capacity to inhibit planktonic bacterial and fungal growth, and their ability to inhibit the formation of or disrupt mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms.

Anti-staphylococcal biofilm activity of miconazoctylium bromide.

We designed and synthesized miconazole analogues containing a substituted imidazolium moiety. The structural modification of the miconazole led to a compound with high potency to prevent the formation and disrupt bacterial biofilms, as a result of accumulation in the biofilm matrix, permeabilization of the bacterial membrane and generation of reactive oxygen species in the cytoplasm.

Effects of stereochemistry, saturation, and hydrocarbon chain length on the ability of synthetic constrained azacyclic sphingolipids to trigger nutrient transporter down-regulation, vacuolation, and cell death.

Constrained analogs containing a 2-hydroxymethylpyrrolidine core of the natural sphingolipids sphingosine, sphinganine, N,N-dimethylsphingosine and N-acetyl variants of sphingosine and sphinganine (C2-ceramide and dihydro-C2-ceramide) were synthesized and evaluated for their ability to down-regulate nutrient transporter proteins and trigger cytoplasmic vacuolation in mammalian cells. In cancer cells, the disruptions in intracellular trafficking produced by these sphingolipids lead to cancer cell death by starvation. Structure activity studies were conducted by varying the length of the hydrocarbon chain, the degree of unsaturation and the presence or absence of an aryl moiety on the appended chains, and stereochemistry at two stereogenic centers.