The Evaluation of DHPMs as Biotoxic Agents on Pathogen Bacterial Membranes

Gawdzik, Barbara; Kowalczyk, Paweł; Koszelewski, Dominik; Brodzka, Anna; Masternak, Joanna; Kramkowski, Karol; Wypych, Aleksandra; Ostaszewski, Ryszard

doi:10.3390/membranes12020238

Cited by 8 publications

(31 citation statements)

References 59 publications

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“…The sensitivity of E. coli strains to the cytotoxic effect of the used compounds and after Fpg protein digestion were as follows: R4 > R2 > R3 > K12. This effect was similar to our previous studies [ 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 49 , 52 ].…”

Section: Results and Discussionsupporting

confidence: 93%

“…Varied inhibitory activity was noted depending on the nature of the substituent in the aromatic ring of the tested compounds. The minimal inhibitory concentration values for each model E. coli R2–R4 and K12 strains were visible on all analysed microplates after the addition of the microbial growth index, resazurin [ 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 49 , 52 ].…”

Section: Results and Discussionmentioning

confidence: 99%

“…Until now, such compounds have not been tested for biological activity against pathogenic E. coli strains, so there is a need to clarify their role [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Functionalised Anodised Aluminium Oxide as a Biocidal Agent

Schabikowski

Laskowska

Kowalczyk

et al. 2022

IJMS

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In this article, we describe the antimicrobial properties of a new composite based on anodic aluminium oxide (AAO) membranes containing propyl-copper-phosphonate units arranged at a predetermined density inside the AAO channels. The samples were prepared with four concentrations of copper ions and tested as antimicrobial drug on four different strains of Escherichia coli (K12, R2, R3 and R4). For comparison, the same strains were tested with three types of antibiotics using the minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than antibiotics such as ciprofloxacin, bleomycin and cloxacillin. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA. We have also observed that the intermolecular distances between the functional units play an important role for the antimicrobial properties of the used material. Hence, we utilised the idea of the 2D solvent to tailor them.

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Section: Results and Discussionsupporting

confidence: 93%

Section: Results and Discussionmentioning

confidence: 99%

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Functionalised Anodised Aluminium Oxide as a Biocidal Agent

Schabikowski

Laskowska

Kowalczyk

et al. 2022

IJMS

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“…All selected analyzed β-phosphonate derivatives ( Figure 3 ) with different substituents located at the phenyl ring are responsible for the change of the topology of bacterial DNA. After digestion with Fpg, approximately 3.5% of oxidative damage was identified, which very strongly indicates oxidative damage in bacterial DNA, similar to the previous observations [ 71 , 72 , 73 , 74 ].…”

Section: Resultssupporting

confidence: 90%

“…The three compounds analyzed were selected for further analysis by modifying their DNA. Modified bacterial DNA was digested with Fpg as previously described [ 70 , 71 ]. All selected analyzed derivatives of β-phosphonate derivatives, including various types of alkoxy groups, substituents located at aromatic rings, and the length of the alkyl chain, can strongly change the bacterial DNA topology.…”

Section: Methodsmentioning

confidence: 99%

Promiscuous Lipase-Catalyzed Knoevenagel–Phospha–Michael Reaction for the Synthesis of Antimicrobial β-Phosphono Malonates

Samsonowicz-Górski

Koszelewski

Kowalczyk

et al. 2022

IJMS

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An enzymatic route for phosphorous–carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant β-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel–phospha–Michael reaction. We carefully analyzed the best conditions for the given reaction: the type of enzyme, temperature, and type of solvent. A series of target compounds was synthesized, with yields ranging from 43% to 93% by enzymatic reaction with Candida cylindracea (CcL) lipase as recyclable and, a few times, reusable catalyst. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The applicability of the same catalyst in the synthesis of β-phosphononitriles is also described. Further, the obtained compounds were validated as new potential antimicrobial agents with characteristic E. coli bacterial strains. The pivotal role of such a group of phosphonate derivatives on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. The impact of the β-phosphono malonate chemical structure on antimicrobial activity was demonstrated. The crucial role of the substituents attached to the aromatic ring on the inhibitory action against selected pathogenic E. coli strains was revealed. Among tested compounds, four β-phosphonate derivatives showed an antimicrobial activity profile similar to that obtained with currently used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained compounds constitute a convenient platform for further chemical functionalization, allowing for a convenient change in their biological activity profile. It should also be noted that the cost of the compounds obtained is low, which may be an attractive alternative to the currently used antimicrobial agents. The observed results are especially important because of the increasing resistance of bacteria to various drugs and antibiotics.

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