Structure–retention behaviour of biologically active fused 1,2,4-triazinones – Correlation with in silico molecular properties

Sztanke, Małgorzata; Tuzimski, Tomasz; Janicka, Małgorzata; Sztanke, Krzysztof

doi:10.1016/j.ejps.2014.12.011

Cited by 13 publications

(29 citation statements)

References 52 publications

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“…All pharmaceutically relevant compounds [19,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] were resynthesized in our laboratory for the current research purposes and their structures, belonging to particular groups, are listed in Table 1. They have been shown to possess mainly promising anticancer [19,[21][22][23][24][25][26][27][28][29][30]32], analgesic [19,21,31,33], antiviral and antihaemolytic [27] activities. Small molecules 1-6 (group I) and 61-65 (group VII) are of particular importance as possible anticancer drug candidates for the treatment of human tumours of lung, cervix, breast and ovary [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, test compounds proved to be in vivo active when investigated in the central nervous system. Among analgesic active and relatively low toxic molecules (8-11, 32, 34, 39, 42, 48, 51 and 53), the structures 8, 42 and 51 have been shown to produce the strongest antinociceptive effect in mice [19,21,31,33]. been shown to possess the remarkable concentration-dependent potency against Herpes simplex virus type 1, while revealing a low toxicity to normal Vero cells and inhibiting the oxidatively-induced haemolysis of erythrocytes [27].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases

Janicka

Sztanke

2020

Molecules

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The permeation of the blood-brain barrier is a very important consideration for new drug candidate molecules. In this research, the reversed-phase liquid chromatography with different columns (Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester) was used to predict the penetration of the blood-brain barrier by 65 newly-synthesized drug-like compounds. The linear free energy relationships (LFERs) model (log BB = c + eE + sS + aA + bB + vV) was established for a training set of 23 congeneric biologically active azole compounds with known experimental log BB (BB = Cblood/Cbrain) values (R2 = 0.9039). The reliability and predictive potency of the model were confirmed by leave-one-out cross validation as well as leave-50%-out cross validation. Multiple linear regression (MLR) was used to develop the quantitative structure-activity relationships (QSARs) to predict the log BB values of compounds that were tested, taking into account the chromatographic lipophilicity (log kw), polarizability and topological polar surface area. The excellent statistics of the developed MLR equations (R2 > 0.8 for all columns) showed that it is possible to use the HPLC technique and retention data to produce reliable blood-brain barrier permeability models and to predict the log BB values of our pharmaceutically important molecules.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases

Janicka

Sztanke

2020

Molecules

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“…The studied compounds have been synthesised and characterised by their spectroscopic data (IR, 1 H NMR, 13 C NMR, EI-MS), sharp melting points, biological (mostly antitumour, antinociceptive activities and antagonism towards adenosine A2A receptors), physico-chemical, drug-likeness properties and lipophilicity indices in correlation studies with in silico pharmacokinetic descriptors as published and patented previously [14][15][16][17][18][19]21]. Furthermore, the range of thermal stability of carbohydrazide-bearing compounds, a mechanism of thermal decomposition and major decomposition products of some of the most active and selective agents with prospective medical use have been determined and described recently [20].…”

Section: Synthesis and Characterisation Of The Investigated Hydrazidementioning

confidence: 99%

“…triazine-3-carbohydrazide (6), 2-(4-oxo-8-phenyl-4,6,7,8-tetrahydroimidazo [2,1- (11) (Figure 1) [14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Biologically important hydrazide-containing fused azaisocytosines as antioxidant agents

Sztanke

2017

Redox Report

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Recent applications of retention modelling in liquid chromatography

Uijl

Schoenmakers

Pirok

et al. 2020

J of Separation Science

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Recent applications of retention modelling in liquid chromatography (2015–2020) are comprehensively reviewed. The fundamentals of the field, which date back much longer, are summarized. Retention modeling is used in retention‐mechanism studies, for determining physical parameters, such as lipophilicity, and for various more‐practical purposes, including method development and optimization, method transfer, and stationary‐phase characterization and comparison. The review focusses on the effects of mobile‐phase composition on retention, but other variables and novel models to describe their effects are also considered. The five most‐common models are addressed in detail, i.e. the log‐linear (linear‐solvent‐strength) model, the quadratic model, the log–log (adsorption) model, the mixed‐mode model, and the Neue–Kuss model. Isocratic and gradient‐elution methods are considered for determining model parameters and the evaluation and validation of fitted models is discussed. Strategies in which retention models are applied for developing and optimizing one‐ and two‐dimensional liquid chromatographic separations are discussed. The review culminates in some overall conclusions and several concrete recommendations.

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Structure–retention behaviour of biologically active fused 1,2,4-triazinones – Correlation with in silico molecular properties

Cited by 13 publications

References 52 publications

Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases

Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases

Biologically important hydrazide-containing fused azaisocytosines as antioxidant agents

Recent applications of retention modelling in liquid chromatography

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