Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids

Kadela-Tomanek, Monika; Jastrzębska, Maria; Chrobak, Elwira; Bębenek, Ewa

doi:10.3390/pharmaceutics15010034

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…The results of these studies are included in Table 1 , and the graphical visualization of the calculated logP values of each compound is shown in Figure 3 and Figure 4 . Such large differences in the obtained values of the lipophilicity parameter were reported before [ 27 , 28 , 29 ] and, as in these previous studies, accurate experimental measurments are needed in order to narrow them down.…”

Section: Discussionmentioning

confidence: 65%

“…It can be concluded that the group of 10-substituted 1,9-diazaphenothiazines is moderately lipophilic compared to the isomeric 1,6-, 1,8-, 2,7 and 3,6-diazaphenothiazines [ 29 , 30 , 31 , 32 , 33 ]. A comparative summary of selected derivatives with the following substituents, hydrogen atom ( A derivatives), allyl ( B derivatives), propargyl ( C derivatives) and dimethylaminopropyl ( D derivatives), is presented in Table 9 and visualized graphically in Figure 5 .…”

Section: Discussionmentioning

confidence: 99%

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Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Morak‐Młodawska

Jeleń

Martula

et al. 2023

IJMS

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Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substituted 1,9-diazaphenothiazines show promising if not impressive in vitro anticancer potential, which is associated with the activation of the mitochondrial apoptosis pathway connected with to induction BAX, forming a channel in MOMP and releasing cytochrome c for the activation of caspases 9 and 3. In this publication, the lipophilicity of previously obtained 1,9-diazaphenothiazines was determined theoretically using various computer programs and experimentally using reverse-phase thin-layer chromatography (RP-TLC) and a standard curve. The study presents other physicochemical, pharmacokinetic, and toxicological properties affecting the bioavailability of the test compounds. ADME analysis was determined in silico using the SwissADME server. Molecular targets studies were identified in silico using the SwissTargetPrediction server. Lipinski’s rule of five, Ghose’s, and Veber’s rules were checked for the tested compounds, confirming their bioavailability.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Morak‐Młodawska

Jeleń

Martula

et al. 2023

IJMS

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“…Among other separation techniques, micellar liquid chromatography (MLC) or micellar electrokinetic chromatography (MEEKC), respectively, in which the mobile phase comprises surfactants that allow better mapping of penetration of molecules through biomembranes can be also be used for lipophilicity determination [ 7 ]. The literature review shows that numerous publications have dealt with the subject of determining the lipophilicity of various bioactive compounds using chromatographic methods [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Lipophilicity Parameters of Antimicrobial and Immunosuppressive Compounds

2023

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Lipophilicity in addition to the solubility, acid-base character and stability is one of the most important physicochemical parameters of a compound required to assess the ADMET properties (absorption, distribution, metabolism, excretion and toxicity) of a bioactive molecule. Therefore, the subject of this work was to determine the lipophilicity parameters of selected antimicrobial and immunosuppressive compounds such as delafloxacin, linezolid, sutezolid, ceftazidime, everolimus and zotarolimus using thin-layer chromatography in reversed phase system (RP-TLC). The chromatographic parameters of lipophilicity (RMW) for tested compounds were determined on different stationary phases: RP18F254, RP18WF254 and RP2F254 using ethanol, acetonitrile, and propan-2-ol as organic modifiers of mobile phases used. Chromatographically established RMW values were compared with partition coefficients obtained by different computational methods (AlogPs, AClogP, AlogP, MlogP, XlogP2, XlogP3, logPKOWWIN, ACD/logP, milogP). Both cluster and principal component analysis (CA and PCA) of the received results allowed us to compare the lipophilic nature of the studied compounds. The sum of ranking differences analysis (SRD) of all lipophilicity parameters was helpful to select the most effective method of determining the lipophilicity of the investigated compounds. The presented results demonstrate that RP-TLC method may be a good tool in determining the lipophilic properties of studied substances. Obtained lipophilic parameters of the compounds can be valuable in the design of their new derivatives as efficient antimicrobial and immunosuppressive agents.

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“…The measure of similarity of two compounds is the Euclidean distance (ED). If the ED distance is similar, it means that the compounds exhibit similar features [63][64][65][66]. As seen in Table S2, the derivatives in different subclusters have the same ED distance, which means that the compounds show high similarity.…”

Section: Discussionmentioning

confidence: 98%

Assessment of Bioavailability Parameters of Mono- and Bistriazole Derivatives of Propynoylbetulin

Kadela-Tomanek,

Sokal,

Stocerz

et al. 2024

Applied Sciences

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Bioavailability describes the properties that determine the passage of a compound through biological barriers. In many cases, bioavailability depends on the lipophilicity of the compound. In this study, the lipophilicity as well as other bioavailability properties of the mono- and bistriazole derivatives of betulin are presented. The lipophilicity was determined using RP-TLC and theoretical methods. The experimental lipophilicity of mono- and bistriazole derivatives is in the range from 4.39 to 7.85 and from 3.75 to 8.83, respectively. The lipophilicity of mono- and bistriazoles is similar, and the logPTLC depends on the type of substituent at the triazole ring. The introduction of a substituent with oxygen and nitrogen atoms decreases lipophilicity. Comparing the experimental and theoretical lipophilicity shows that the milogP and XLOGP3 programs best reproduce the experimental values. The in silico-determined pharmacokinetic parameters show that monotriazole derivatives could be used as oral drugs while bistriazoles show low availability after oral administration. Triazoles could be used as transdermal drugs. The analysis of in silico bioavailability parameters shows that the type of substituent at the triazole ring influences the pharmacokinetic properties, while the number of triazole rings slightly affects the bioavailability properties of the compound.

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Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids

Cited by 5 publications

References 43 publications

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Assessment of Lipophilicity Parameters of Antimicrobial and Immunosuppressive Compounds

Assessment of Bioavailability Parameters of Mono- and Bistriazole Derivatives of Propynoylbetulin

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