Highly Effective Biocides against Reveal New Mechanistic Insights Across Gram-Negative Bacteria.

is a major nosocomial pathogen that persists in healthcare settings despite rigorous disinfection protocols due to intrinsic mechanisms conferring resistance. We sought to systematically assess cationic biocide efficacy against this pathogen using a panel of multidrug-resistant clinical isolates. Our studies revealed widespread resistance to commercial cationic disinfectants that are the current standard of care, raising concerns about their efficacy.

Deriving Novel Quaternary Ammonium Compound Disinfectant Scaffolds from a Natural Product: Mechanistic Insights of the Quaternization of Ianthelliformisamine C.

In the search for novel quaternary ammonium compound (QAC) disinfectants that can evade bacterial resistance, we turned to natural products as a source of inspiration. Herein we used natural product ianthelliformisamine C as a scaffold to design a small library of QACs. We first synthesized ianthelliformisamine C via an amide coupling that allowed for facile purification without the need for protecting groups.

Total Synthesis and Biological Investigation of Mindapyrroles A and B.

In the search for antibacterial compounds that can overcome drug resistant species, molecules that enact novel or polypharmacological mechanisms of action (MoA) are needed. As a preliminary foray into molecules of this background, the total synthesis of mindapyrroles A and B was undertaken leveraging a biomimetic approach. Following their synthesis, they and their monomer pyoluteorin were tested against a range of pathogenic bacteria in minimum inhibitory concentration assays to confirm their activity.

Quaternary Phosphonium Compound Unveiled as a Potent Disinfectant against Highly Resistant Clinical Isolates.

is classified as a highest threat pathogen, urgently necessitating novel antimicrobials that evade resistance to combat its spread. Quaternary ammonium compounds (QACs) have afforded a valuable first line of defense against antimicrobial resistant pathogens as broad-spectrum amphiphilic disinfectant molecules. However, a paucity of innovation in this space has driven the emergence of QAC resistance.

Trivalent sulfonium compounds (TSCs): Tetrahydrothiophene-based amphiphiles exhibit similar antimicrobial activity to analogous ammonium-based amphiphiles.

Recent advances in the development of quaternary ammonium compounds (QACs) have focused on new structural motifs to increase bioactivity, but significantly less studied has been the change from ammonium- to sulfonium-based disinfectants. Herein, we report the synthesis of structurally analogous series of quaternary ammonium and trivalent sulfonium compounds (TSCs). The bioactivity profiles of these compounds generally mirror each other, and the antibacterial activity of sulfonium-based THT-18 was found to be comparable to the commercial disinfectant, BAC.

Metallocene QACs: The Incorporation of Ferrocene Moieties into monoQAC and bisQAC Structures.

Inspired by the incorporation of metallocene functionalities into a variety of bioactive structures, particularly antimicrobial peptides, we endeavored to broaden the structural variety of quaternary ammonium compounds (QACs) by the incorporation of the ferrocene moiety. Accordingly, 23 ferrocene-containing mono- and bisQACs were prepared in high yields and tested for activity against a variety of bacteria, including Gram-negative strains and a panel of clinically isolated MRSA strains. Ferrocene QACs were shown to be effective antiseptics with some displaying single-digit micromolar activity against all bacteria tested, demonstrating yet another step in the expansion of structural variety of antiseptic QACs.

More QACs, more questions: Recent advances in structure activity relationships and hurdles in understanding resistance mechanisms.

Quaternary ammonium compounds (QACs) are a class of antimicrobials that have been around for over a century; nevertheless, they have found continued renewal in the structures to which they can be appended. Ranging from antimicrobial polymers to adding novel modes of action to existing antibiotics, QACs have found ongoing use due to their potent properties. However, resistance against QACs has begun to emerge, and the mechanism of resistance is still only partially understood.

Broadening Activity of Polymyxin by Quaternary Ammonium Grafting.

Bacterial pathogens continue to impose a tremendous health burden across the globe. Here, we describe a novel series of polymyxin-based agents grafted with membrane-active quaternary ammonium warheads to combine two important classes of Gram-negative antimicrobial scaffolds. The goal was to deliver a targeted quaternary ammonium warhead onto the surface of bacterial pathogens using the outer membrane homing properties of polymyxin.

Further Investigations into Rigidity-Activity Relationships in BisQAC Amphiphilic Antiseptics.

Thirty-six biscationic quaternary ammonium compounds were efficiently synthesized in one step to examine the effect of molecular geometry of two-carbon linkers on antimicrobial activity. The synthesized compounds showed strong antimicrobial activity against a panel of both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). While the linker geometry showed only a modest correlation with antimicrobial activity, several of the synthesized bisQACs are promising potential antiseptics due to good antimicrobial activity (MIC≤2 μM) and their higher therapeutic indices compared to previously reported QACs.

Ester- and amide-containing multiQACs: Exploring multicationic soft antimicrobial agents.

Quaternary ammonium compounds (QACs) are ubiquitous antiseptics whose chemical stability is both an aid to prolonged antibacterial activity and a liability to the environment. Soft antimicrobials, such as QACs designed to decompose in relatively short times, show the promise to kill bacteria effectively but not leave a lasting footprint. We have designed and prepared 40 soft QAC compounds based on both ester and amide linkages, in a systematic study of mono-, bis-, and tris-cationic QAC species.

Optimized aerial applications of two resmethrin formulations against caged Anopheles quadrimaculatus.

Optimized aerial applications were conducted to assess the efficacy of 2 formulations of resmethrin (Scourge 18-54, Aqua-Scourge 10-30) for control of caged adult Anopheles quadrimaculatus. Micronair AU4000 rotary atomizers were employed to apply the chemical. Both compounds were applied at 0.

Utility of the Bender Visual-Motor Gestalt Test-Second Edition in the assessment of attention-deficit/hyperactivity disorder.

This study examined the use of the Bender Visual-Motor Gestalt Test-Second Edition (BGT-II) with children diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). Previous research has examined the relationship of ADHD and visual-motor functioning based on overall developmental scores or specific emotional indicators. Although several studies have examined the relationship of the previous edition of the BGT-II and ADHD symptoms, psychometric issues associated with the original edition limit the validity of the results.

Validity of two selected-item short forms of the WAIS-III in an intellectually deficient sample.

Various short forms of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III; D. Wechsler, 1997) have been investigated, but limited information is available regarding the usefulness of any WAIS-III abbreviation with intellectually deficient individuals. Our study compared the validities of two WAIS-III selected-item short forms in a sample of 59 individuals with full scale IQs (FSIQs) of 79 or lower.