Physicochemical evaluation of new tetrahydroacridine and iodobenzoic acid hybrids as the next step in the design of potential drugs for treating Alzheimer's disease

Kręcisz, Paweł; Czarnecka, Kamila; Szymański, Paweł

doi:10.1002/bmc.4906

Cited by 2 publications

(1 citation statement)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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]. Although, lipophilicity is commonly applied for prediction of absorption, distribution, metabolism, and excretion (ADME) properties, usually with the octanol-water system or RPLC, several studies pointed out that these systems are oversimplified to simulate membrane partitioning [13].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

Thin-Layer Chromatography Gradient Optimization Strategy for Wet Load Adsorption Flash Chromatography

Kręcisz

Czarnecka

Szymański

2021

Journal of Chromatographic Science

View full text Add to dashboard Cite

Chromatography is one of the most popular methods for the separation of compounds in modern pharmaceutical industry and science. Despite the extensive use of the reversed phase chromatography in analytical and preparative applications, the normal phase adsorption chromatography has a special place in purifying post-reaction mixtures or the separation of natural extracts, especially in wet load mode, because of simplicity and high velocity of preparation. Complex mixtures, more difficult to separate, require gradient methods to obtain better results of separations. These methods can be developed by external software, but the automatic methods are often not very accurate and the negative impact of wet load application on separation quality is considerable in them. Therefore, we present the thin-layer chromatography (TLC) gradient optimization strategy for wet load separations to obtain repeatable results of separations for different compounds without worrying about negative impact of wet loading on separation quality. The strategy provides information about an elution model of desired compound, which is used to develop the gradient method. The strategy also allows to standardize the separation length, because gradient methods performed by the TLC gradient optimization strategy have a very similar duration time in column volumes. The method can also be simply scaled because of using the column volume as a base unit in calculations.

show abstract

Physicochemical evaluation of new tetrahydroacridine and iodobenzoic acid hybrids as the next step in the design of potential drugs for treating Alzheimer's disease

Cited by 2 publications

References 19 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

Thin-Layer Chromatography Gradient Optimization Strategy for Wet Load Adsorption Flash Chromatography

Contact Info

Product

Resources

About