Drug repurposing to overcome microbial resistance

Jampílek, Josef

doi:10.1016/j.drudis.2022.05.006

Cited by 27 publications

(14 citation statements)

References 187 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, for example, the effects on the parasites Onchocerca or Toxoplasma have been described recently [ 44 , 45 ]. Important derivatives include, for example, niclosamide, which, in addition to its anthelmintic activity, has proven to be an important aid in the fight against cancer growth [ 46 ] as well as an antimicrobial agent [ 47 ]. The activity of all these compounds is closely related to the presence of halogen in the molecule.…”

Section: Introductionmentioning

confidence: 99%

Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics

Pindjakova

Pilařová

Pauk

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

A series of eleven benzylated intermediates and eleven target compounds derived from salicylanilide were tested against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as reference strains and against three clinical isolates of methicillin-resistant S. aureus (MRSA) and three isolates of vancomycin-resistant E. faecalis. In addition, the compounds were evaluated against Mycobacterium tuberculosis H37Ra and M. smegmatis ATCC 700084. The in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line THP-1. The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. The benzylated intermediates were found to be completely biologically inactive. Of the final eleven compounds, according to the number of amide groups in the molecule, eight are diamides, and three are triamides that were inactive. 5-Chloro-2-hydroxy-N-[(2S)- 4-(methylsulfanyl)-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (3e) and 5-chloro-2-hydroxy-N-[(2S)-(4-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino)pentan-2-yl)benzamide (3f) showed the broadest spectrum of activity against all tested species/isolates comparable to the used standards (ampicillin and isoniazid). Six diamides showed high antistaphylococcal activity with MICs ranging from 0.070 to 8.95 μM. Three diamides showed anti-enterococcal activity with MICs ranging from 4.66 to 35.8 μM, and the activities of 3f and 3e against M. tuberculosis and M. smegmatis were MICs of 18.7 and 35.8 μM, respectively. All the active compounds were microbicidal. It was observed that the connecting linker between the chlorsalicylic and 4-CF3-anilide cores must be substituted with a bulky and/or lipophilic chain such as isopropyl, isobutyl, or thiabutyl chain. Anticancer activity on THP-1 cells IC50 ranged from 1.4 to >10 µM and increased with increasing lipophilicity.

show abstract

Section: Introductionmentioning

confidence: 99%

Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics

Pindjakova

Pilařová

Pauk

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Phenothiazines are also known for their ability to interact with and damage the cell wall, which has fatal consequences for the microorganism [ 44 , 45 ]. Therefore, the bacterial suspensions were treated by compounds 6a , 6e , 6g , 6j and 6k (4× MIC) for 1 h. The uptake of crystal violet was expressed as a percentage compared to the original crystal violet solution.…”

Section: Resultsmentioning

confidence: 99%

“…Phenothiazines, like quinolines, are multi-target agents, i.e., they have the ability to affect several different targets, leading to the death of treated microorganisms. Quinolines are known to be able to inhibit, for example, the respiratory chain (possessing a similar mechanism of action to bedaquiline [ 46 , 47 , 48 , 49 ]), sulphur metabolic pathways [ 50 ] or mycobacterial FtsZ protein [ 51 ]; phenothiazines, in addition to the aforementioned ability to interact with the bacterial membrane, have the ability to inhibit the respiratory chain, dissipate the membrane potential, reduce the level of ATP, increase oxidative stress or increase the level of intracellular ions [ 44 , 45 , 52 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives

Kisiel-Nawrot

Pindjakova²,

Latocha³

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

A new method for modifying the structure of tetracyclic quinobenzothiazinium derivatives has been developed, allowing introduction of various substituents at different positions of the benzene ring. The method consists of reacting appropriate aniline derivatives with 5,12-(dimethyl)thioquinantrenediinium bis-chloride. A series of new quinobenzothiazine derivatives was obtained with propyl, allyl, propargyl and benzyl substituents in 9, 10 and 11 positions, respectively. The structure of the obtained compounds was analyzed by 1H and 13C NMR (HSQC, HMBC) and X-ray analysis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). In addition, all the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. 9-Benzyloxy-5-methyl-12H-quino [3,4-b][1,4]benzothiazinium chloride (6j), 9-propoxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6a) and 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6d) demonstrated high activity against the entire tested microbial spectrum. The activities of the compounds were comparable with oxacillin, tetracycline and ciprofloxacinagainst staphylococcal strains and with rifampicin against both mycobacterial strains. Compound 6j had a significant effect on the inhibition of bacterial respiration as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity, but also bactericidal activity. Preliminary in vitro cytotoxicity screening of the compounds performed using normal human dermal fibroblasts (NHDF) proved that the tested compounds showed an insignificant cytotoxic effect on human cells (IC50 > 37 µM), making these compounds interesting for further investigation. Moreover, the intermolecular similarity of novel compounds was analyzed in the multidimensional space (mDS) of the structure/property-related in silico descriptors by means of principal component analysis (PCA) and hierarchical clustering analysis (HCA), respectively. The distance-oriented structure/property distribution was related with the experimental lipophilic data.

show abstract

“…Thus, Jampilek summarized the causes of antimicrobial resistance, discussed drug repurposing strategy in seeking novel anti-infective drugs. 14 …”

Section: Repurposing Drugs As Anti-infective Therapiesmentioning

confidence: 99%

Drug repurposing: An effective strategy to accelerate contemporary drug discovery

Zhan

Ouyang

2022

Drug Discovery Today

View full text Add to dashboard Cite

Drug repurposing to overcome microbial resistance

Cited by 27 publications

References 187 publications

Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics

Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics

Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives

Drug repurposing: An effective strategy to accelerate contemporary drug discovery

Contact Info

Product

Resources

About