Identification of 2,4-Di--Butylphenol as an Antimicrobial Agent Against Bacteria from Rwandan Propolis.

Background/objectives: Acne is the most prevalent dermatological condition among humans, affecting approximately 80% of adolescents during puberty. To date, numerous compounds have been used for acne treatment, including erythromycin ointments and antiseptics, with varying degrees of success. The emergence of erythromycin-resistant strains has spurred the search for new antimicrobial agents, particularly from natural sources.

Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives.

In an effort to expand the spectrum of the antibacterial activity of pleuromutilin, a series of amine- and polyamine-linked analogues were prepared and evaluated for activities against a panel of microorganisms. Simple C-22-substituted amino esters or diamines , , , and , as well as two unusual amine-linked bis-pleuromutilin examples and , displayed variable levels of activity towards ATCC 25923 and methicillin-resistant , but with no detectable activities towards Gram-negative bacteria. Fortunately, the incorporation of a longer-chain triamine or polyamine (spermine) at C-22 did afford analogues (, ) that exhibited activity towards both ATCC 25923 and ATCC 25922 with MIC 6.

Computational Methods Reveal a Series of Cyclic and Linear Lichenysins and Surfactins from the Vietnamese Marine Sediment-Derived Strain G222.

The strain G222, isolated from a Vietnamese marine sediment, was confidently identified by 16 rRNA gene sequencing. Its AcOEt crude extract was successfully analyzed using non-targeted LC-MS/MS analysis, and molecular networking, leading to a putative annotation of its chemical diversity thanks to spectral libraries from GNPS and metabolite structure prediction obtained from SIRIUS combined with the bioinformatics tool conCISE (Consensus Annotation Propagation of Elucidations). This dereplication strategy allowed the identification of an interesting cluster of a series of putative cyclic and linear lipopeptides of the lichenysin and surfactin families.

Antimicrobial Indole-3-Carboxamido-Polyamine Conjugates Target Bacterial Membranes and Are Antibiotic Potentiators.

Small molecules that can restore the action of legacy antibiotics toward drug-resistant bacteria represent an area of ongoing research interest. We have previously reported indole-3-glyoxylamido and indole-3-acetamido-polyamine conjugates that exhibit intrinsic activity toward bacterial and fungal species, and the ability to enhance the action of doxycycline toward the Gram-negative bacteria ; however, these desirable activities were commonly associated with unfavorable cytotoxicity and/or red blood cell hemolytic properties. In this paper, we report the synthesis and biological investigation of a new class of α,ω-di(indole-3-carboxamido)polyamine derivatives, leading to the identification of several analogues that exhibit antimicrobial- and antibiotic-potentiating activities without detectable cytotoxic or hemolytic properties.

Preliminary SAR of Novel Pleuromutilin-Polyamine Conjugates.

While pleuromutilin () and its clinically available derivatives (-) are highly effective against Gram-positive bacteria, they remain inactive against many pathogenic Gram-negative bacteria due to the efflux pump AcrAB-TolC. In an effort to broaden the spectrum of activity of pleuromutilin (), we developed a series of novel pleuromutilin-polyamine conjugates (-) which exhibited promising intrinsic antimicrobial properties, targeting both Gram-positive and Gram-negative bacteria, including , methicillin-resistant (MRSA), and , along with the fungal strain , and were devoid of cytotoxic and hemolytic properties with the exception of one conjugate. Furthermore, this series displayed moderate to low antibiotic potentiation of legacy antibiotics doxycycline and erythromycin, with three conjugates enhancing the activity four-fold in combination with doxycycline.

Indole-3-Acetamido-Polyamines as Antimicrobial Agents and Antibiotic Adjuvants.

The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the action of ineffective antibiotics. Herein, we report the synthesis of a new class of indole-3-acetamido-polyamine conjugates that were evaluated for antimicrobial activities against a panel of bacteria and two fungi, and for the ability to enhance the action of doxycycline against and erythromycin against . Compounds , , , , , , , , and exhibited strong growth inhibition of methicillin-resistant (MRSA) and , with minimum inhibitory concentrations (MIC) typically less than 0.

Exploration of Bis-Cinnamido-Polyamines as Intrinsic Antimicrobial Agents and Antibiotic Enhancers.

The marine natural product ianthelliformisamine C is a bis-cinnamido substituted spermine derivative that exhibits intrinsic antimicrobial properties and can enhance the action of doxycycline towards the Gram-negative bacterium . As part of a study to explore the structure-activity requirements of these activities, we have synthesized a set of analogues that vary in the presence/absence of methoxyl group and bromine atoms and in the polyamine chain length. Intrinsic antimicrobial activity towards , methicillin-resistant (MRSA) and the fungus was observed for only the longest polyamine chain examples of non-brominated analogues while all examples bearing either one or two bromine atoms were active.

Structure-Activity Relationship Studies of Indolglyoxyl-Polyamine Conjugates as Antimicrobials and Antibiotic Potentiators.

Antibiotic resistance is a growing global health threat, requiring urgent attention. One approach to overcome antibiotic resistance is to discover and develop new antibiotic enhancers, molecules that work with legacy antibiotics to enhance their efficacy against resistant bacteria. Our previous screening of a library of purified marine natural products and their synthetic analogues led to the discovery of an indolglyoxyl-spermine derivative that exhibited intrinsic antimicrobial properties and was also able to potentiate the action of doxycycline towards the difficult to treat, Gram-negative bacterium .

Investigation of Naphthyl-Polyamine Conjugates as Antimicrobials and Antibiotic Enhancers.

As part of our search for new antimicrobials and antibiotic enhancers, a series of naphthyl- and biphenyl-substituted polyamine conjugates have been synthesized. The structurally-diverse library of compounds incorporated variation in the capping end groups and in the length of the polyamine (PA) core. Longer chain (PA-3-12-3) variants containing both 1-naphthyl and 2-naphthyl capping groups exhibited more pronounced intrinsic antimicrobial properties against methicillin-resistant (MRSA) (MIC ≤ 0.

α,ω-Diacyl-Substituted Analogues of Natural and Unnatural Polyamines: Identification of Potent Bactericides That Selectively Target Bacterial Membranes.

In this study, α-ω-disubstituted polyamines exhibit a range of potentially useful biological activities, including antimicrobial and antibiotic potentiation properties. We have prepared an expanded set of diarylbis(thioureido)polyamines that vary in central polyamine core length, identifying analogues with potent methicillin-resistant (MRSA), , and growth inhibition properties, in addition to the ability to enhance action of doxycycline towards Gram-negative bacterium . The observation of associated cytotoxicity/hemolytic properties prompted synthesis of an alternative series of diacylpolyamines that explored aromatic head groups of varying lipophilicity.

Investigation of α,ω-Disubstituted Polyamine-Cholic Acid Conjugates Identifies Hyodeoxycholic and Chenodeoxycholic Scaffolds as Non-Toxic, Potent Antimicrobials.

With the increased incidence of antibiotic resistance, the discovery and development of new antibacterials is of increasing importance and urgency. The report of the natural product antibiotic squalamine in 1993 has stimulated a lot of interest in the study of structurally simplified cholic acid-polyamine derivatives. We report the synthesis of a focused set of deoxycholic acid-polyamine conjugates and the identification of hyodeoxycholic acid derivatives as being potently active towards MRSA and some fungal strains, but with no attendant cytotoxicity or hemolytic properties.

Nanoarchitectonics of Electrically Activable Phosphonium Self-Assembled Monolayers to Efficiently Kill and Tackle Bacterial Infections on Demand.

Prosthetic implants are widely used in dentistry and orthopedics and, as a result, infections can occur which cause their removal. Therefore, it is essential to propose methods of eradicating the bacteria that remain on the prosthesis during treatment. For this purpose, it is necessary to develop surfaces whose antibacterial activity can be controlled.

Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in the Democratic Republic of the Congo: emergence of highly resistant pfdhfr/pfdhps alleles.

Background: In 2005, the Democratic Republic of the Congo (DRC) switched to artesunate/amodiaquine as the first-line antimalarial in response to increasing sulfadoxine/pyrimethamine resistance and adopted intermittent preventive treatment using sulfadoxine/pyrimethamine in pregnancy.

Objectives: To determine the prevalence of molecular markers of sulfadoxine/pyrimethamine resistance in southwestern DRC 10 years after the new policy was instituted.

Methods: From March 2014 to December 2015, blood samples were collected from symptomatic patients presenting to outpatient centres in urban and rural areas.