Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches

Ciura, Krzesimir; Fedorowicz, Joanna; Andrić, Filip; Greber, Katarzyna E.; Gurgielewicz, Alina; Sawicki, Wiesław; Sączewski, Jarosław

doi:10.3390/ijms20215288

Cited by 32 publications

(27 citation statements)

References 29 publications

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“…Moreover, due to the presence of permanent positive charge within the triazolium moiety, Saf dyes were employed as ionization tags suitable for peptide identification [6]. chromatography (RPLC) and micellar electrokinetic chromatography (MEKC) [8]. The importance of drug candidate characterization in terms of their physicochemical properties is critical, since these analyses support selection of the most promising compounds [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Affinity of Fluoroquinolone–Safirinium Dye Hybrids to Phospholipids Estimated by IAM-HPLC

et al. 2020

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Nowadays, fluoroquinolones (FQs) constitute one of the most important classes of antibiotics. FQs are used to treat infections caused by Gram-positive and Gram-negative species. A set of fluoroquinolone–Safirinium dye hybrids has been synthesized in our laboratory as potential new dual-action antibacterial agents. In the present study we have evaluated how such a modification influences the affinity of FQs to phospholipids. The immobilized artificial membrane (IAM) high-performance liquid chromatography (IAM-HPLC) was used as a tool for the determination of phospholipids partitioning. The obtained results indicate that the fluoroquinolone–Safirinium dye hybrids, especially the SafiriniumP conjugates, display significantly lower affinity to phospholipids than the parent FQs. Despite the fact that the hybrid structures comprise a quaternary nitrogen atom and hence are permanently charged, the attractive electrostatic interactions between the solutes and negatively charged phospholipids do not occur or occur at a lesser extent than in the case of the unmodified FQs. Since affinity of FQs to phospholipids involves molecular mechanism, which is not entirely determined by lipophilicity, assessment of phospholipid partitioning should be considered at the early stage of the development of new FQ antibiotics.

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Section: Introductionmentioning

confidence: 99%

Affinity of Fluoroquinolone–Safirinium Dye Hybrids to Phospholipids Estimated by IAM-HPLC

et al. 2020

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“…To study the possibility of using computer models to calculate LogP ow [ 21 ], miLogP ow values were calculated for the same substances by the Molinspiration package [ 22 ], which is an online tool available at . The method for logP prediction developed at Molinspiration (miLogP ow ) is based on group contributions.…”

Section: Methodsmentioning

confidence: 99%

N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation

et al. 2020

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The wide spread of pathogens resistance requires the development of new antimicrobial agents capable of overcoming drug resistance. The main objective of the study is to elucidate the effect of substitutions in tris(1H-indol-3-yl)methylium derivatives on their antibacterial activity and toxicity to human cells. A series of new compounds were synthesized and tested. Their antibacterial activity in vitro was performed on 12 bacterial strains, including drug resistant strains, that were clinical isolates or collection strains. The cytotoxic effect of the compounds was determined using an test with HPF-hTERT (human postnatal fibroblasts, immortalized with hTERT) cells. The activity of the obtained compounds depended on the carbon chain length. Derivatives with C5–C6 chains were more active. The minimum inhibitory concentration (MIC) of the most active compound on Gram-positive bacteria, including MRSA, was 0.5 μg/mL. Compounds with C5–C6 chains also revealed high activity against Staphylococcus epidermidis (1.0 and 0.5 μg/mL, respectively) and moderate activity against Gram-negative bacteria Escherichia coli (8 μg/mL) and Klebsiella pneumonia (2 and 8 μg/mL, respectively). However, they have no activity against Salmonella cholerasuis and Pseudomonas aeruginosa. The most active compounds revealed higher antibacterial activity on MRSA than the reference drug levofloxacin, and their ratio between antibacterial and cytotoxic activity exceeded 10 times. The data obtained provide a basis for further study of this promising group of substances.

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“…Lipophilicity, defined as the affinity of a compound towards nonpolar phase, is also significant for potential drug evaluation [ 29 ]. The log P parameter is linked to the absorption, distribution, metabolism and excretion processes [ 30 , 31 ]. It has been shown that lipophilicity that is too high is associated with undesirable properties, such as accumulation of the compound in the adipose tissue [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide

Gach

Olejniczak

Krężel

et al. 2021

IJMS

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Phthalides are bioactive compounds that naturally occur in the family Apiaceae. Considering their potentially versatile applications, it is desirable to determine their physical properties, activity and metabolic pathways. This study aimed to examine the utility of whole-cell biocatalysts for obtaining 3-butyl-3-hydroxyphthalide, which is the metabolite formulated during mammalian metabolism of 3-n-butylidenephthalide. We performed transformations using 10 strains of fungi, five of which efficiently produced 3-butyl-3-hydroxyphthalide. The product yield, determined by high-performance liquid chromatography, reached 97.6% when Aspergillus candidus AM 386 was used as the biocatalyst. Increasing the scale of the process resulted in isolation yields of 29–45% after purification via reversed-phase thin layer chromatography, depending on the strain of the microorganism used. We proposed different mechanisms for product formation; however, hydration of 3-n-butylidenephthalide seems to be the most probable. Additionally, all phthalides were tested against clinical strains of Candida albicans using the microdilution method. Two phthalides showed a minimum inhibitory concentration, required to inhibit the growth of 50% of organisms, below 50 µg/mL. The 3-n-butylidenephthalide metabolite was generally inactive, and this feature in combination with its low lipophilicity suggests its involvement in the detoxification pathway. The log P value of tested compounds was in the range of 2.09–3.38.

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Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches

Cited by 32 publications

References 29 publications

Affinity of Fluoroquinolone–Safirinium Dye Hybrids to Phospholipids Estimated by IAM-HPLC

Affinity of Fluoroquinolone–Safirinium Dye Hybrids to Phospholipids Estimated by IAM-HPLC

N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation

Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide

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