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1.
Biomedicines ; 12(5)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38791021

RESUMEN

Vitamin A, an essential micronutrient, is integral to various biological processes crucial for organismal development and maintenance. Dietary sources of vitamin A encompass preformed retinol, retinyl esters, and provitamin A carotenoids. Retinoic acid (RA), a key component, plays pivotal roles in vision, cell proliferation, apoptosis, immune function, and gene regulation. Drug repurposing, an effective strategy for identifying new therapeutic applications for existing drugs, has gained prominence in recent years. This review seeks to provide a comprehensive overview of the current research landscape surrounding retinoids and drug repurposing. The scope of this review encompasses a comprehensive examination of retinoids and their potential for repurposing in various therapeutic contexts. Despite their efficacy in treating dermatological conditions, concerns about toxicity persist, driving the search for safer and more potent retinoids. The molecular mechanisms underlying retinoid activity involve binding to retinoic acid receptors (RARs) and retinoid X receptors (RXRs), leading to transcriptional regulation of target genes. This review seeks to shed light on the possibilities for repurposing retinoids to cover a wider spectrum of therapeutic uses by exploring recent scientific progress. It also aims to offer a more comprehensive understanding of the therapeutic prospects of retinoids and the broader impact of drug repositioning in contemporary medicine.

2.
J Chromatogr A ; 1656: 462552, 2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34571283

RESUMEN

Naturally occurring molecules are excellent sources of lead compounds. A series of oleanolic acid (OA) derivatives previously synthesized in our laboratory, which show promising antitumor activity, have been analyzed in terms of lipophilicity evaluation applying chromatographic and computational approaches. Retention data obtained on three reversed-phase liquid chromatography stationary phases (RP-HPLC) and immobilized artificial membrane chromatography (IAM-HPLC) were compared with computational methods using chemometric tools such as cluster analysis, principal component analysis and sum of ranking differences. To investigate the molecular mechanism of retention quantitive structure retention relationship analysis was performed, based on the genetic algorithm coupled with multiple linear regression (GA-MLR). The obtained results suggested that the ionization potential of studied molecules significantly affects their retention in classical RP-HPLC. In IAM-HPLC additionally, polarizability-related descriptors also play an essential role in that process. The lipophilicity indices comparison shows significant differences between the computational lipophilicity and chromatographically determined ones.


Asunto(s)
Ácido Oleanólico , Triterpenos , Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Ácido Oleanólico/análogos & derivados
3.
J Pharm Biomed Anal ; 188: 113423, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32623315

RESUMEN

The development of high-throughput methods for the estimation of physicochemical and biological properties of drug candidates is highly desired in the pharmaceutical landscape. Affinity to plasma protein is one of the most important biological properties, which should be taken under concern during the design and assessment of future potential medicines. The main goal of this study was to develop a quantitative retention-activity relationship model, with rationalized in vivo and in silico approach to predict the affinity to human serum albumin (HSA), which is one of the most important plasma proteins. To achieve this goal, a set of 27 chemically diverse drugs with known affinity to HSA were analyzed by micellar electrokinetic chromatography (MEKC). The proposed model for HSA affinity assessment was based on retention in hexadecyltrimethylmonium bromide (CTAB) pseudostationary phase and chemically advanced template search (CATS) pharmacophore descriptors. The comparison of various regression methods, namely multiple linear regression (MLR), partial least squares regression (PLS), orthogonal partial least squares (OPLS), and support vector machine (SVM) were performed to develop a model with highest predictability. The obtained models are suitable for the prediction of drug affinity to human serum albumin using retention factor determined by MEKC and CATS descriptors, and only slightly differ in terms of coefficients of determination, Q2 value calculated using leave-one-out cross-validation technique and root-mean-squared error of cross-validation (RMSECV) as well as root-mean-square error in prediction (RMSEP) obtained by external validation.


Asunto(s)
Micelas , Albúmina Sérica Humana , Cetrimonio , Análisis de los Mínimos Cuadrados , Modelos Lineales
4.
Curr Comput Aided Drug Des ; 16(2): 93-103, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30727911

RESUMEN

BACKGROUND: Pharmacological and physicochemical classification of bases' selected analogues of nucleic acids is proposed in the study. OBJECTIVE: Structural parameters received by the PCM (Polarizable Continuum Model) with several types of calculation methods for the structures in vacuo and in the aquatic environment together with the huge set of extra molecular descriptors obtained by the professional software and literature values of biological activity were used to search the relationships. METHODS: Principal Component Analysis (PCA) together with Factor Analysis (FA) and Multiple Linear Regressions (MLR) as the types of the chemometric approach based on semi-empirical ab initio molecular modeling studies were performed. RESULTS: The equations with statistically significant descriptors were proposed to demonstrate both the common and differentiating characteristics of the bases' analogues of nucleic acids based on the quantum chemical calculations and biological activity data. CONCLUSION: The obtained QSAR models can be used for predicting and explaining the activity of studied molecules.


Asunto(s)
Ácidos Nucleicos , Nucleósidos/análogos & derivados , Modelos Moleculares , Nucleósidos/química , Análisis de Componente Principal , Relación Estructura-Actividad Cuantitativa , Teoría Cuántica
5.
Molecules ; 24(23)2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31779124

RESUMEN

The lipophilicity of a molecule is a well-recognized as a crucial physicochemical factor that conditions the biological activity of a drug candidate. This study was aimed to evaluate the lipophilicity of isoxazolo[3,4-b]pyridine-3(1H)-ones and their N1-substituted derivatives, which demonstrated pronounced antifungal activities. Several methods, including reversed-phase thin layer chromatography (RP-TLC), reversed phase high-performance liquid chromatography (RP-HPLC), and micellar electrokinetic chromatography (MEKC), were employed. Furthermore, the calculated logP values were estimated using various freely and commercially available software packages and online platforms, as well as density functional theory computations (DFT). Similarities and dissimilarities between the determined lipophilicity indices were assessed using several chemometric approaches. Principal component analysis (PCA) indicated that other features beside lipophilicity affect antifungal activities of the investigated derivatives. Quantitative-structure-retention-relationship (QSRR) analysis by means of genetic algorithm-partial least squares (GA-PLS)-was implemented to rationalize the link between the physicochemical descriptors and lipophilicity. Among the studied compounds, structure 16 should be considered as the best starting structure for further studies, since it demonstrated the lowest lipophilic character within the series while retaining biological activity. Sum of ranking differences (SRD) analysis indicated that the chromatographic approach, regardless of the technique employed, should be considered as the best approach for lipophilicity assessment of isoxazolones.


Asunto(s)
Antifúngicos/química , Piridinas/química , Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Fase Inversa/métodos , Cromatografía en Capa Delgada/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Lípidos/química , Análisis de Componente Principal/métodos , Relación Estructura-Actividad Cuantitativa
6.
J Pharm Biomed Anal ; 176: 112767, 2019 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-31398505

RESUMEN

Chromatographic properties of sixteen ß-blockers were studied using planar chromatography. The aim of presented study was to investigate influence of different organic solvents (acetonitrile, methanol, dioxin and tetrahydrofurane) on ß-blockers' retention on C18 bonded silica gel stationary phase. Group of sixteen, diverse in terms of structure, beta blockers was used as a model set. The main goal of this study was to compare chromatographically estimated lipophilicity parameters with values obtained with the use of computational methods. Furthermore, in order to understand molecular mechanisms of retention better, quantitative structure-retention relationships (QSRR) analysis was performed. The next step was focused on application of chromatographically obtained lipophilicity parameters for prediction of protein binding (PB), based on quantitative retention-activity relationships (QRAR) approach. The obtained results showed that reversed-phase thin layer chromatography (RP-TLC), especially with tetrafydrofurane used as an organic modifier of mobile phase, is a useful tool for lipophilicity estimation, as well as for prediction of ß-blockers' biological properties. The QRAR model included C0 parameters for tetrahydrofuran-water as a mobile phase, as well as maximal projection area, and can be easily applied for prediction of systematically synthesized ß-blockers structures' PB.


Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Descubrimiento de Drogas/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Químicos , Antagonistas Adrenérgicos beta/química , Cromatografía de Fase Inversa/métodos , Cromatografía en Capa Delgada/métodos , Estructura Molecular , Unión Proteica , Relación Estructura-Actividad Cuantitativa , Solventes/química
7.
Comb Chem High Throughput Screen ; 22(2): 97-112, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31020936

RESUMEN

BACKGROUND: A set of ß-lactam antibiotics, aminoglycoside antibiotics, and tetracycline antibiotics were proposed and analyzed with the use of Quantitative Structure-Activity Relationships (QSAR) method. OBJECTIVE: The characterization of selected antimicrobial compounds in terms of both physicochemical and pharmacological on the basis of calculations of quantum mechanics and possessed biological activity data. METHODS: During the study, Multiple Linear Regression (MLR) supported with Factor Analysis (FA) and Principal Component Analysis (PCA) was made, as the types of proposed chemometric approach; the semi-empirical level of in silico molecular modeling was used for calculations and comparison of molecular descriptors both in a vacuum and in the aquatic environment. RESULTS: The relationships between structure and microbiological activity enabled the characterization and description of the analyzed molecules using statistically significant descriptors belonging in most cases to different structural, geometric and electronic elements defining at the same time the properties of the studied three different classes of examined antibiotics. CONCLUSION: The chemometric methods used revealed the influence of some of the elements of structures examined molecules belonging to main antibiotics classes and responsible for the antimicrobial activity.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Relación Estructura-Actividad Cuantitativa , Teoría Cuántica , Investigación Empírica , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Análisis de Componente Principal
8.
Biochim Biophys Acta Biomembr ; 1861(1): 93-99, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30463703

RESUMEN

Short cationic lipopeptides are amphiphilic molecules that exhibit antimicrobial activity mainly against Gram-positives. These compounds bind to bacterial membranes and disrupt their integrity. Here we examine the structure-activity relation (SAR) of lysine-based lipopeptides, with a prospect to rationally design more active compounds. The presented study aims to explain how antimicrobial activity of lipopeptides is affected by the charge of lipopeptide headgroup and the length of lipopeptide acyl chain. The obtained SAR models suggest that the lipophilicity of short synthetic cationic lipopeptides is the major factor that determines their antimicrobial activities. In order to link the differences in antimicrobial activity to the mechanism of action of lipopeptides containing one and two hydrophobic chains, we additionally performed molecular dynamic (MD) simulations. By using combined coarse-grained and all-atom simulations we also show that these compounds neither affect the organization of the membrane lipids nor aggregate to form separate phases. These results, along with the onset of antimicrobial activity of lipopeptides well below the critical micelle concentration (CMC), indicate that lipopeptides do not act in a simple detergent-like manner.


Asunto(s)
Membrana Celular/efectos de los fármacos , Lipopéptidos/química , Simulación de Dinámica Molecular , Relación Estructura-Actividad , Antibacterianos/química , Péptidos Catiónicos Antimicrobianos/química , Simulación por Computador , Detergentes/química , Electrones , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Membrana Dobles de Lípidos/química , Lisina/química , Lípidos de la Membrana/química , Micelas , Pruebas de Sensibilidad Microbiana , Albúmina Sérica Humana/química
9.
Med Chem Res ; 27(10): 2279-2286, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30294193

RESUMEN

A set of psychoactive drugs has been analyzed with the use of quantitative structure-activity/property relationships methods. The purpose of this study was to demonstrate both the common and differentiating characteristics of the above-mentioned chemical compounds, physicochemical as well as pharmacological based on the quantum chemical calculations and selected biological activity data and chromatographic retention parameters. During the study, the ab initio model of molecular modeling was performed and PCA, FA, and MLR as the types of chemometric approach. QSAR/QSPR models were proposed based on chosen statistically significant descriptors. The relationship between the structure and biological activity data was able to class and describe the psychoactive properties of the molecules studied. The applied chemometric approaches revealed the influential features of tested structures responsible for their pharmacological activity together with some additional physicochemical properties.

10.
Comb Chem High Throughput Screen ; 21(7): 468-475, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30147010

RESUMEN

BACKGROUND: A set of antibiotic fluoroquinolones with confirmed antimicrobial activity were analyzed with the use of two types of quantum chemical calculation methods and quantitative structure-activity relationships (QSAR). OBJECTIVE: The purpose of this study was to demonstrate the common and differentiating characteristics of the above-mentioned chemical compounds alike physicochemically as well as pharmacologically based on the quantum chemical calculations and microbiological activity data. METHODS: During the study PCA and MLR analysis were performed, as the types of proposed chemometric approach. The semi-empirical level of in silico molecular modeling was performed for calculations of molecular descriptors. RESULTS: QSAR models were proposed based on chosen descriptors. The relationship between the structure and microbiological activity and physicochemical parameters data was able to class and describe them with the use of statistically significant molecular descriptors. CONCLUSION: The applied chemometric approaches revealed the influential features of tested structures responsible for the antimicrobial activity of analyzed compounds.


Asunto(s)
Antibacterianos/farmacología , Fluoroquinolonas/farmacología , Mycobacterium avium/efectos de los fármacos , Relación Estructura-Actividad Cuantitativa , Teoría Cuántica , Antibacterianos/química , Fluoroquinolonas/química , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular
11.
Amino Acids ; 50(3-4): 479-485, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29264738

RESUMEN

In this study, we investigated the influence of molecular descriptors of cationic lipopeptides on their antimicrobial activity and hemolytic properties. The quantitative structure-activity relationship and quantitative structure-property relationship models were constructed. The antimicrobial, hemolytic and retention data were used as dependent variable and structural parameters as the independent ones. The obtained results suggest that the chromatographic indexes can be employed for prediction of antibacterial activity and that lipopeptides present nonspecific interaction between erythrocytes and bacterial membranes.


Asunto(s)
Antibacterianos/química , Péptidos Catiónicos Antimicrobianos/química , Lipopéptidos/química , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/patogenicidad , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Lipopéptidos/farmacología , Relación Estructura-Actividad Cuantitativa , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad
12.
J Pharm Biomed Anal ; 149: 70-79, 2018 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-29101818

RESUMEN

Lipophilicity of compound is well known as vital physicochemical property of a molecule, which determines its biological activity. Nonetheless, the assessment of a lipophilicity is still problematic and focuses attention of scientists. Although, the shake-flask method is still considered as a gold standard for experimental determination of lipophilicity, currently the chromatographic approach is mostly used. Among chromatographic methods used for lipophilicity assessment, thin layer chromatography (TLC) is still one of the most popular tools. The main goal of this study was to compare classical reversed-phase thin layer chromatography (RP-TLC) and micellar TLC as potential tools for lipophilicity assessment. Micellar liquid chromatography has significantly lover environment impact than classical reversed-phase liquid chromatography. Additionally comparison of cationic and anionic surfactants (CTAB and SDS), which have different chemical properties, as modifiers of mobile phase in micellar TLC were investigated. The Quantitative Structure-Retention Relationships (QSRR) approach was used in order to present molecular mechanisms of retention in investigated chromatographic systems. The study was based on chemically diverse model set compounds, with a proved therapeutic or toxic potential. According to obtained results the micellar TLC with CTAB as surfactant can be recommended to logP prediction. The obtained QSRR models indicated that adsorption of CTAB monomers on CN modified surface of silica gel and the silanol-quaternary ammonium interactions are possible. Consequently, the reduction of interaction between molecules and free silanol, contributes to the improvement of logP predictions. These result were confirmed by regression and classification methods.


Asunto(s)
Cromatografía de Fase Inversa/métodos , Micelas , Relación Estructura-Actividad Cuantitativa , Tensoactivos/química , Aniones/química , Cationes/química , Cetrimonio , Compuestos de Cetrimonio/química , Cromatografía en Capa Delgada/métodos , Análisis de Componente Principal , Compuestos de Amonio Cuaternario/química , Análisis de Regresión , Silanos/química , Dodecil Sulfato de Sodio/química , Solubilidad
13.
J Pharm Biomed Anal ; 143: 214-221, 2017 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-28641198

RESUMEN

The objective of this paper is to build QSRR/QSAR model for predicting the blood-brain barrier (BBB) permeability. The obtained models are based on salting-out thin layer chromatography (SOTLC) constants and calculated molecular descriptors. Among chromatographic methods SOTLC was chosen, since the mobile phases are free of organic solvent. As consequences, there are less toxic, and have lower environmental impact compared to classical reserved phases liquid chromatography (RPLC). During the study three stationary phase silica gel, cellulose plates and neutral aluminum oxide were examined. The model set of solutes presents a wide range of log BB values, containing compounds which cross the BBB readily and molecules poorly distributed to the brain including drugs acting on the nervous system as well as peripheral acting drugs. Additionally, the comparison of three regression models: multiple linear regression (MLR), partial least-squares (PLS) and orthogonal partial least squares (OPLS) were performed. The designed QSRR/QSAR models could be useful to predict BBB of systematically synthesized newly compounds in the drug development pipeline and are attractive alternatives of time-consuming and demanding directed methods for log BB measurement. The study also shown that among several regression techniques, significant differences can be obtained in models performance, measured by R2 and Q2, hence it is strongly suggested to evaluate all available options as MLR, PLS and OPLS.


Asunto(s)
Barrera Hematoencefálica , Cromatografía Liquida , Cromatografía en Capa Delgada , Análisis de los Mínimos Cuadrados , Modelos Lineales , Relación Estructura-Actividad Cuantitativa
14.
Acta Pol Pharm ; 73(1): 247-54, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27008819

RESUMEN

Rx-to-OTC switch is a global occurrence, which aims to promote patients' responsible self-treatment of minor ailments. Many countries could benefit from such self-treatment and reduce their rising health care costs by allowing citizens to avoid the need for a physician's consultations. What must be noted however, is that the inappropriate use of over-the-counter medicines can have also a darker side. Potential problems arising from OTC use might include: increased costs of treating complications resulting from not proper use or abuse, or possible interactions with the other medications, that patients take for chronic diseases. To maintain the desired level of patient safety, relieving one working group (the medical profession) from an existing obligation should be associated with the need for increased involvement and/or authorizations from other working groups. Professional pharmacists are already globally recognized as being trained in the field of health condition assessment. This paper presents an objective case study of current pharmaceutical law and thus, may serve as a starting point for an responsible discussion regarding the institution of a new class of drugs understood as pharmacist-only.


Asunto(s)
Legislación de Medicamentos , Medicamentos sin Prescripción , Costos de la Atención en Salud , Humanos , Farmacéuticos , Polonia , Rol Profesional , Sistema de Registros
15.
Med Chem ; 12(5): 404-11, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26732114

RESUMEN

Mass spectrometry (LC-MS or LC-MS/MS) appears in all phases of drug discovery and drug development areas. Starting with the screening and identification of a therapeutic agent and further measuring its in vivo and in vitro properties include: absorption, distribution, metabolism, excretion and toxicity (ADMET) and also pharmacokinetic (PK) and pharmacodynamic (PD) quantitative parameters of drug candidate. Mass spectrometry also serves as a necessary tool also to confirm purity and stability of analyzed new chemical entities (NCEs)/new molecular entities (NMEs) as well as for the analysis of degradation products from the synthesis and following on every stages of drug discovery.


Asunto(s)
Cromatografía Liquida/métodos , Descubrimiento de Drogas/métodos , Espectrometría de Masas/métodos , Animales , Células CACO-2 , Humanos , Farmacocinética , Toxicocinética
16.
Med Chem Res ; 24: 372-382, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25589825

RESUMEN

Thirty-three compounds belonging to the sympatholytics and sympathomimetics were analyzed during the study. The biological activity data for the parameters of binding affinity to the α1- and α2-adrenergic receptors together with parameters of the logarithm of the partition coefficient n-octanol/water (log P) were performed using a semi-empirical calculations methods for isolated molecules (in vacuo) and for the molecules placed in an aqueous environment. Additionally, the chromatographic retention data were used as extra dependent variables of the structural parameters for a part of the considered compounds. Finally, all those groups of parameters were analyzed using MLR, PCA, and FA methods for the classification of studied compounds according to their chemical structures and pharmacological activity to the adrenoceptors.

17.
Comb Chem High Throughput Screen ; 16(8): 603-17, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23547602

RESUMEN

The parameters of lipophilicity for three different groups of drugs (twelve analgesics drugs, eleven cardiovascular system drugs, and thirty six compounds characterized by divergent pharmacological activity) were experimentally determined by HPLC methods as well as calculated using various computer programs (HyperChem, ACD/Labs, ChemAxon, Dragon and VCCLab). The relationships between experimental (chromatographic) parameters of lipophilicity (log k and log kw) and the chemical structure of the studied compounds, and their comparison due to their lipophilic and hydrophilic character were presented. Moreover, the experimental and calculated values of parameters of lipophilicity were correlated and compared. Finally, both these groups of parameters of lipophilicity were analyzed using PCA or FA methods for the classification of studied compounds according to their chemical structures and pharmacological activity.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Preparaciones Farmacéuticas/química , Analgésicos/química , Fármacos Cardiovasculares/química , Análisis Factorial , Lípidos/química , Análisis de Componente Principal
18.
Med Chem ; 9(4): 517-25, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23140578

RESUMEN

Relationship between activity and structure of the selected 4-chloro-2-mercapto-5-methylbenzensulfonamide derivatives with their potential anticancer activity was studied. Lipophilicity was determined using two distinct chromatographic methods. Moreover, geometry of studied compounds was optimized with the help of HyperChem software to obtain some molecular descriptors. Reversed-phase and micellar liquid chromatography lipophilicity parameters together with theoretically calculated parameters were used to study the relationship between structure and activity. Principal component analysis performed firstly on activity data and secondly on molecular parameters revealed similar results, which allowed us to divide studied set of compounds into three distinct clusters differing in both structure and activity. Moreover, stepwise regression analysis led to statistically significant equation describing potential anticancer activity of studied derivatives based on nuclear energy and log P (partition coefficient) of compounds.


Asunto(s)
Antineoplásicos/química , Compuestos de Sulfhidrilo/química , Sulfonamidas/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Modelos Moleculares , Análisis de Componente Principal , Relación Estructura-Actividad Cuantitativa , Análisis de Regresión , Compuestos de Sulfhidrilo/farmacología , Sulfonamidas/farmacología
19.
Int J Mol Sci ; 13(6): 6665-6678, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22837656

RESUMEN

Pharmacological and physicochemical classification of the furan and thiophene amide derivatives by multiple regression analysis and partial least square (PLS) based on semi-empirical ab initio molecular modeling studies and high-performance liquid chromatography (HPLC) retention data is proposed. Structural parameters obtained from the PCM (Polarizable Continuum Model) method and the literature values of biological activity (antiproliferative for the A431 cells) expressed as LD(50) of the examined furan and thiophene derivatives was used to search for relationships. It was tested how variable molecular modeling conditions considered together, with or without HPLC retention data, allow evaluation of the structural recognition of furan and thiophene derivatives with respect to their pharmacological properties.


Asunto(s)
Amidas/química , Furanos/química , Tiofenos/química , Antineoplásicos/química , Línea Celular Tumoral , Química Farmacéutica , Cromatografía , Cromatografía Líquida de Alta Presión , Humanos , Análisis de los Mínimos Cuadrados , Modelos Moleculares , Conformación Molecular , Teoría Cuántica , Análisis de Regresión , Agua/química
20.
J Sep Sci ; 33(11): 1546-57, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20373294

RESUMEN

A series of newly synthesized 1,3-purinodiones with potential anticonvulsant activity, exhibiting affinity to adenosine A(1) and/or A(2A) receptors, were subjected to micellar LC (MLC) with SDS as micelle-forming agent and n-propanol as organic modifier. Two C18 silica-based columns were employed in MLC: a particle one and a monolithic. In parallel, those derivatives were also analyzed in RP-LC on four silica-based columns and on an immobilized artificial membrane column. The correlations between the relevant logarithms of the retention factors of analytes obtained in MLC, immobilized artificial membrane and RP-LC systems on the one hand, and the calculated log P (clog P) and log D values (clog D) on the other, were examined. The level of the correlations of retention data from MLC and RP-LC systems with clog P and clog D obtained is similar but it could be stressed that MLC allows increasing the speed of analysis and using only one mobile phase. Moreover, there is no need of applying an extrapolation procedure in lipophilicity determination. Therefore, the MLC systems, providing chromatographic data in a fast and efficient manner, were demonstrated as promising alternatives to the classical RP-LC systems to estimate the lipophilicity of drugs and drug candidates.


Asunto(s)
Cromatografía Liquida/métodos , Lípidos/química , Micelas , Purinas/química , Técnicas de Química Analítica/métodos , Química Farmacéutica/métodos , Modelos Químicos , Dióxido de Silicio , Solventes/química , Agua/química , Xenobióticos/química
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