Narrow-spectrum antibacterial agents

Melander, Roberta J.; Zurawski, Daniel V.; Melander, Christian

doi:10.1039/c7md00528h

Cited by 173 publications

(162 citation statements)

References 88 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…If the causative agent of the infection is known, the use of narrow-spectrum antibiotics can alleviate some of these problems. The development of narrow-spectrum antibiotics that do not cause cross-resistance in non-targeted microbes and elicit less collateral damage upon the host microbiome is an attractive approach to fight multidrug-resistance infections [ 12 ]. It is also expected that new drugs will be non-toxic in vivo at therapeutic doses.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4,4′-(4-Formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections

Delancey

Allison

et al. 2020

Antibiotics

View full text Add to dashboard Cite

Acinetobacter baumannii has emerged as one of the most lethal drug-resistant bacteria in recent years. We report the synthesis and antimicrobial studies of 25 new pyrazole-derived hydrazones. Some of these molecules are potent and specific inhibitors of A. baumannii strains with a minimum inhibitory concentration (MIC) value as low as 0.78 µg/mL. These compounds are non-toxic to mammalian cell lines in in vitro studies. Furthermore, one of the potent molecules has been studied for possible in vivo toxicity in the mouse model and found to be non-toxic based on the effect on 14 physiological blood markers of organ injury.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis of 4,4′-(4-Formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections

Delancey

Allison

et al. 2020

Antibiotics

View full text Add to dashboard Cite

show abstract

“…These screens resulted in the discovery of many antibiotics exhibiting both broad spectrum, such as streptomycin (19), and mycobacterium-specific activity, including isoniazid, pyrazinamide, ethionamide, ethambutol (4), and bedaquiline (20). Recently, Gramspecific (21)(22)(23)(24) and pathogen-specific (25,26) antibiotic discovery were also proven to be successful, leading to the identification of narrow spectrum compounds, including some that are active only against A. baumannii (27)(28)(29). As more candidate compounds are revealed through screening, there will be a need for better methods to elucidate their mechanism of action (MOA) in A. baumannii.…”

mentioning

confidence: 99%

Bacterial Cytological Profiling as a Tool To Study Mechanisms of Action of Antibiotics That Are Active against Acinetobacter baumannii

Htoo

Brumage

Chaikeeratisak

et al. 2019

Antimicrob Agents Chemother

View full text Add to dashboard Cite

An increasing number of multidrug-resistant Acinetobacter baumannii (MDR-AB) infections have been reported worldwide, posing a threat to public health. The establishment of methods to elucidate the mechanism of action (MOA) of A. baumannii-specific antibiotics is needed to develop novel antimicrobial therapeutics with activity against MDR-AB. We previously developed bacterial cytological profiling (BCP) to understand the MOA of compounds in Escherichia coli and Bacillus subtilis. Given how distantly related A. baumannii is to these species, it was unclear to what extent it could be applied. Here, we implemented BCP as an antibiotic MOA discovery platform for A. baumannii. We found that the BCP platform can distinguish among six major antibiotic classes and can also subclassify antibiotics that inhibit the same cellular pathway but have different molecular targets. We used BCP to show that the compound NSC145612 inhibits the growth of A. baumannii via targeting RNA transcription. We confirmed this result by isolating and characterizing resistant mutants with mutations in the rpoB gene. Altogether, we conclude that BCP provides a useful tool for MOA studies of antibacterial compounds that are active against A. baumannii.

show abstract

“…The most active compounds (11b, 11d, and 11g) had an activity similar to that of the reference antibiotic, exhibited very low cytotoxicity, and were inactive against the other bacteria assayed. This makes them potential leads for the development of narrow spectrum antibiotics against M. tuberculosis, where long-term treatments with broad spectrum antibiotics entail an increased risk of damaging the gut microbiota and promoting the appearance of resistant genes [45].…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Antibacterial Activity of Difluoromethyl Cinnamoyl Amides

et al. 2020

View full text Add to dashboard Cite

Series of novel amides of isoferulic acid, where the phenolic hydroxyl was replaced by a difluoromethyl group, were synthesized and their in vitro antibacterial activities assayed against fourteen bacterial strains (six Gram-positive and eight Gram-negative). A one-pot methodology was developed to obtain the 3′-(difluoromethyl)-4′-methoxycinnamoyl amides using Deoxofluor® as a fluorinating agent. The N-isopropyl, N-isopentyl, and N-(2-phenylethyl) amides 11b, 11d and 11g were the most active and selective against Mycobacterium smegmatis (MIC = 8 µg/mL) with 11b and 11g displaying negligible or no cytotoxicity against HepG2 and A549 cells. Thirteen analogs of N-isopropylamide 11b were also synthesized and their antibacterial activity assayed. Results show that the difluoromethyl moiety enhanced antibacterial activity and selectivity towards M. smegmatis, changing the microorganism inhibition profile of the parent compound. The selectivity exhibited by some of the compounds towards M. smegmatis makes them potential leads in the search for new narrow spectrum antibiotics against M. tuberculosis.

show abstract

Narrow-spectrum antibacterial agents

Cited by 173 publications

References 88 publications

Synthesis of 4,4′-(4-Formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections

Synthesis of 4,4′-(4-Formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections

Bacterial Cytological Profiling as a Tool To Study Mechanisms of Action of Antibiotics That Are Active against Acinetobacter baumannii

Synthesis and Antibacterial Activity of Difluoromethyl Cinnamoyl Amides

Contact Info

Product

Resources

About