TY  - JOUR
AU  - Tot, Kristina
AU  - Lazić, Anita
AU  - Đaković-Sekulić, Tatjana
PY  - 2020
PY  - 2020
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6
AB  - In this study, lipophilicity of 21 cycloalkylspiro-5-hidantoins was assessed. The overall goal of lipophilicity evaluation is preliminary investigation which should result in a decrease of the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity assessment was done by reversed-phase thin-layer chromatography and in silico methods. Chromatographic analyses were performed on C-18 modified thin-layer of silica gel with a two-component mobile phase consisting of water and organic solvent (acetonitrile, acetone, dioxane, or tetrahydrofuran) in different ratios. The chromatographic lipophilicities (R (M) (0)) were discussed and compared with computational log Ps calculated with various algorithms as well as in silico ADMET descriptors using linear regression and multivariate approach (hierarchical cluster analysis and principal component analysis). A high correlation was obtained between R (M) (0) values and calculated log P indicating a strong relationship between the variables. Multivariate data analysis enabled the comparison of the chemical structures, lipophilicity, pharmacokinetic predictors and toxicity of the investigated compounds.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins
EP  - 933
IS  - 19-20
SP  - 925
VL  - 43
DO  - 10.1080/10826076.2020.1856137
ER  - 

@article{
author = "Tot, Kristina and Lazić, Anita and Đaković-Sekulić, Tatjana",
year = "2020, 2020",
abstract = "In this study, lipophilicity of 21 cycloalkylspiro-5-hidantoins was assessed. The overall goal of lipophilicity evaluation is preliminary investigation which should result in a decrease of the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity assessment was done by reversed-phase thin-layer chromatography and in silico methods. Chromatographic analyses were performed on C-18 modified thin-layer of silica gel with a two-component mobile phase consisting of water and organic solvent (acetonitrile, acetone, dioxane, or tetrahydrofuran) in different ratios. The chromatographic lipophilicities (R (M) (0)) were discussed and compared with computational log Ps calculated with various algorithms as well as in silico ADMET descriptors using linear regression and multivariate approach (hierarchical cluster analysis and principal component analysis). A high correlation was obtained between R (M) (0) values and calculated log P indicating a strong relationship between the variables. Multivariate data analysis enabled the comparison of the chemical structures, lipophilicity, pharmacokinetic predictors and toxicity of the investigated compounds.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins",
pages = "933-925",
number = "19-20",
volume = "43",
doi = "10.1080/10826076.2020.1856137"
}

Tot, K., Lazić, A.,& Đaković-Sekulić, T.. (2020). A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 43(19-20), 925-933.
https://doi.org/10.1080/10826076.2020.1856137

Tot K, Lazić A, Đaković-Sekulić T. A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins. in Journal of Liquid Chromatography & Related Technologies. 2020;43(19-20):925-933.
doi:10.1080/10826076.2020.1856137 .

Tot, Kristina, Lazić, Anita, Đaković-Sekulić, Tatjana, "A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins" in Journal of Liquid Chromatography & Related Technologies, 43, no. 19-20 (2020):925-933,
https://doi.org/10.1080/10826076.2020.1856137 . .

TY  - CONF
AU  - Tot, Kristina A.
AU  - Lazić, Anita M.
AU  - Đaković-Sekulić, Tatjana Lj.
PY  - 2019
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/7465
AB  - Spirohidantoins represent a pharmacologically important class of compounds. Many of
them display activities against a wide range of biological targets1
. A recent study shows
that a wide range of biological activities of spirohydantoin derivatives strongly depends
upon their structure. Hence it is important to understand their properties, particularly the
properties of newly synthesized derivatives. One of the most important properties for
biological activity is lipophilicity. Lipophilicity is responsible for pharmacokinetics, and
hence important for further development of potentially active compounds. The aim of
this study is to determine the chromatographic retention parameter of the new
synthesized spirohydantoin derivatives as a measure of their lipophilicity.
Chromatographic retention parameters of investigated compounds have been determined
by reversed-phase thin-layer chromatography on C-18 modified silica gel. Mobile
phases were two-component mixtures of water and aprotic organic solvents (i.e.
acetonitrile, acetone, dioxane, and tetrahydrofuran).
Quantitative structure-retention relationship2 (QSRR) was used for assessment of
relationships between chromatographic retention parameters, RM
0
, and calculated
partition coefficients of the molecule, log P. For the calculation of log P and additional
molecular descriptors were used several software packages (Dragon and ChemDraw) in
addition to online internet modules Molinspiration (https://www.molinspiration.com/)
and ADMETlab (http://admet.scbdd.com/).
PB  - Belgrade : Serbian Chemical Society
C3  - Book of abstracts / Seventh Conference of the Young Chemists of Serbia, Belgrade, 2nd November 2019
T1  - QSRR prediction of the chromatographic retention behaviour of spirohydantoin derivatives
SP  - 118
UR  - https://hdl.handle.net/21.15107/rcub_technorep_7465
ER  - 

@conference{
author = "Tot, Kristina A. and Lazić, Anita M. and Đaković-Sekulić, Tatjana Lj.",
year = "2019",
abstract = "Spirohidantoins represent a pharmacologically important class of compounds. Many of
them display activities against a wide range of biological targets1
. A recent study shows
that a wide range of biological activities of spirohydantoin derivatives strongly depends
upon their structure. Hence it is important to understand their properties, particularly the
properties of newly synthesized derivatives. One of the most important properties for
biological activity is lipophilicity. Lipophilicity is responsible for pharmacokinetics, and
hence important for further development of potentially active compounds. The aim of
this study is to determine the chromatographic retention parameter of the new
synthesized spirohydantoin derivatives as a measure of their lipophilicity.
Chromatographic retention parameters of investigated compounds have been determined
by reversed-phase thin-layer chromatography on C-18 modified silica gel. Mobile
phases were two-component mixtures of water and aprotic organic solvents (i.e.
acetonitrile, acetone, dioxane, and tetrahydrofuran).
Quantitative structure-retention relationship2 (QSRR) was used for assessment of
relationships between chromatographic retention parameters, RM
0
, and calculated
partition coefficients of the molecule, log P. For the calculation of log P and additional
molecular descriptors were used several software packages (Dragon and ChemDraw) in
addition to online internet modules Molinspiration (https://www.molinspiration.com/)
and ADMETlab (http://admet.scbdd.com/).",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Book of abstracts / Seventh Conference of the Young Chemists of Serbia, Belgrade, 2nd November 2019",
title = "QSRR prediction of the chromatographic retention behaviour of spirohydantoin derivatives",
pages = "118",
url = "https://hdl.handle.net/21.15107/rcub_technorep_7465"
}

Tot, K. A., Lazić, A. M.,& Đaković-Sekulić, T. Lj.. (2019). QSRR prediction of the chromatographic retention behaviour of spirohydantoin derivatives. in Book of abstracts / Seventh Conference of the Young Chemists of Serbia, Belgrade, 2nd November 2019
Belgrade : Serbian Chemical Society., 118.
https://hdl.handle.net/21.15107/rcub_technorep_7465

Tot KA, Lazić AM, Đaković-Sekulić TL. QSRR prediction of the chromatographic retention behaviour of spirohydantoin derivatives. in Book of abstracts / Seventh Conference of the Young Chemists of Serbia, Belgrade, 2nd November 2019. 2019;:118.
https://hdl.handle.net/21.15107/rcub_technorep_7465 .

Tot, Kristina A., Lazić, Anita M., Đaković-Sekulić, Tatjana Lj., "QSRR prediction of the chromatographic retention behaviour of spirohydantoin derivatives" in Book of abstracts / Seventh Conference of the Young Chemists of Serbia, Belgrade, 2nd November 2019 (2019):118,
https://hdl.handle.net/21.15107/rcub_technorep_7465 .

TY  - JOUR
AU  - Tot, Kristina
AU  - Lazić, Anita
AU  - Božić, Biljana
AU  - Mandić, Anamarija
AU  - Đaković-Sekulić, Tatjana
PY  - 2019
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4111
AB  - Hydantois have been identified as constituents of a number of pharmacologically active molecules. In the present study, we have examined in vitro antiproliferative activity against human colon cancer cell lines HCT-116 of three series of 3-(4-substituted benzyl)-hydantoins with various substituent attached in position 5 of the hydantoin ring. Since the investigated compounds have recently been synthesized and show antiproliferative activity, a good understanding of the properties of the potential drug responsible for their pharmacokinetics is an important goal for their further development. One of the important properties is lipophilicity. Lipophilicity has been assessed by reversed-phase liquid chromatography (high-performance thin-layer chromatography and high-pressure liquid chromatography) by means of direct and indirect (using calibration curve) methods. Chromatographic lipophilicity indices in addition to calculated logP values were compared by hierarchical cluster analysis. The linear solvation energy relationship approach was used to understand and compare the types and relative strength of the molecular interactions that occur in the chromatographic as well as in the n-octanol-water partitioning systems. Finally, correlation between in silico pharmacokinetic predictors and antiproliferative activity was examined. Preliminary quantitative structure-activity relationship modeling indicates that pharmacokinetic predictors capture only one-quarter of all chemical features that are important for antiproliferative activity itself. Among selected descriptors are chromatographic lipophilicity indices.
PB  - Wiley, Hoboken
T2  - Biomedical Chromatography
T1  - QSAR characterization of new synthesized hydantoins with antiproliferative activity
IS  - 8
VL  - 33
DO  - 10.1002/bmc.4539
ER  - 

@article{
author = "Tot, Kristina and Lazić, Anita and Božić, Biljana and Mandić, Anamarija and Đaković-Sekulić, Tatjana",
year = "2019",
abstract = "Hydantois have been identified as constituents of a number of pharmacologically active molecules. In the present study, we have examined in vitro antiproliferative activity against human colon cancer cell lines HCT-116 of three series of 3-(4-substituted benzyl)-hydantoins with various substituent attached in position 5 of the hydantoin ring. Since the investigated compounds have recently been synthesized and show antiproliferative activity, a good understanding of the properties of the potential drug responsible for their pharmacokinetics is an important goal for their further development. One of the important properties is lipophilicity. Lipophilicity has been assessed by reversed-phase liquid chromatography (high-performance thin-layer chromatography and high-pressure liquid chromatography) by means of direct and indirect (using calibration curve) methods. Chromatographic lipophilicity indices in addition to calculated logP values were compared by hierarchical cluster analysis. The linear solvation energy relationship approach was used to understand and compare the types and relative strength of the molecular interactions that occur in the chromatographic as well as in the n-octanol-water partitioning systems. Finally, correlation between in silico pharmacokinetic predictors and antiproliferative activity was examined. Preliminary quantitative structure-activity relationship modeling indicates that pharmacokinetic predictors capture only one-quarter of all chemical features that are important for antiproliferative activity itself. Among selected descriptors are chromatographic lipophilicity indices.",
publisher = "Wiley, Hoboken",
journal = "Biomedical Chromatography",
title = "QSAR characterization of new synthesized hydantoins with antiproliferative activity",
number = "8",
volume = "33",
doi = "10.1002/bmc.4539"
}

Tot, K., Lazić, A., Božić, B., Mandić, A.,& Đaković-Sekulić, T.. (2019). QSAR characterization of new synthesized hydantoins with antiproliferative activity. in Biomedical Chromatography
Wiley, Hoboken., 33(8).
https://doi.org/10.1002/bmc.4539

Tot K, Lazić A, Božić B, Mandić A, Đaković-Sekulić T. QSAR characterization of new synthesized hydantoins with antiproliferative activity. in Biomedical Chromatography. 2019;33(8).
doi:10.1002/bmc.4539 .

Tot, Kristina, Lazić, Anita, Božić, Biljana, Mandić, Anamarija, Đaković-Sekulić, Tatjana, "QSAR characterization of new synthesized hydantoins with antiproliferative activity" in Biomedical Chromatography, 33, no. 8 (2019),
https://doi.org/10.1002/bmc.4539 . .

TY  - CONF
AU  - Đaković-Sekulić, Tatjana
AU  - Smolinski, Adam
AU  - Tot, Kristina
AU  - Lazić, Anita
PY  - 2017
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/7464
AB  - In this poster presentation the retention data of new cycloalkane-5-spirohydantoins bearing a substituted benzyl group in position 3 of the heterocyclic ring have been examined (Figure 1). Previously the intermolecular interactions of the crystal structures of

cycloalkane-S-spirohydantoins with halo-

In

geno substituted benzyl group (R = Cl and

Br) in position 3 had been studied [1].

Besides, the eflect of R substituent on the absorption UV-Vis spectra of cyclopen-tanespiro-S-hydantoins (2] had been studied,

100.
PB  - Budapest : Research Centre for Natural Sciences, Institute of Excellence, Hungarian Academy of Sciences
C3  - Book of Abstracts / Conferentia Chemometrica 2017, Gyöngyös-Farkasmály, Hungary, September 03-06, 2017
T1  - Lipophilicity assessment and chromatographic characterization of new spirohydantoin derivatives potential anticonvulsant agents
SP  - P09
UR  - https://hdl.handle.net/21.15107/rcub_technorep_7464
ER  - 

@conference{
author = "Đaković-Sekulić, Tatjana and Smolinski, Adam and Tot, Kristina and Lazić, Anita",
year = "2017",
abstract = "In this poster presentation the retention data of new cycloalkane-5-spirohydantoins bearing a substituted benzyl group in position 3 of the heterocyclic ring have been examined (Figure 1). Previously the intermolecular interactions of the crystal structures of

cycloalkane-S-spirohydantoins with halo-

In

geno substituted benzyl group (R = Cl and

Br) in position 3 had been studied [1].

Besides, the eflect of R substituent on the absorption UV-Vis spectra of cyclopen-tanespiro-S-hydantoins (2] had been studied,

100.",
publisher = "Budapest : Research Centre for Natural Sciences, Institute of Excellence, Hungarian Academy of Sciences",
journal = "Book of Abstracts / Conferentia Chemometrica 2017, Gyöngyös-Farkasmály, Hungary, September 03-06, 2017",
title = "Lipophilicity assessment and chromatographic characterization of new spirohydantoin derivatives potential anticonvulsant agents",
pages = "P09",
url = "https://hdl.handle.net/21.15107/rcub_technorep_7464"
}

Đaković-Sekulić, T., Smolinski, A., Tot, K.,& Lazić, A.. (2017). Lipophilicity assessment and chromatographic characterization of new spirohydantoin derivatives potential anticonvulsant agents. in Book of Abstracts / Conferentia Chemometrica 2017, Gyöngyös-Farkasmály, Hungary, September 03-06, 2017
Budapest : Research Centre for Natural Sciences, Institute of Excellence, Hungarian Academy of Sciences., P09.
https://hdl.handle.net/21.15107/rcub_technorep_7464

Đaković-Sekulić T, Smolinski A, Tot K, Lazić A. Lipophilicity assessment and chromatographic characterization of new spirohydantoin derivatives potential anticonvulsant agents. in Book of Abstracts / Conferentia Chemometrica 2017, Gyöngyös-Farkasmály, Hungary, September 03-06, 2017. 2017;:P09.
https://hdl.handle.net/21.15107/rcub_technorep_7464 .

Đaković-Sekulić, Tatjana, Smolinski, Adam, Tot, Kristina, Lazić, Anita, "Lipophilicity assessment and chromatographic characterization of new spirohydantoin derivatives potential anticonvulsant agents" in Book of Abstracts / Conferentia Chemometrica 2017, Gyöngyös-Farkasmály, Hungary, September 03-06, 2017 (2017):P09,
https://hdl.handle.net/21.15107/rcub_technorep_7464 .

TY  - CONF
AU  - Tot, Jadranka A.
AU  - Tot, Kristina A.
AU  - Đaković-Sekulić, Tatjana Lj.
AU  - Lazić, Anita M.
AU  - Ušćumlić, Gordana S.
PY  - 2016
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6784
AB  - Predmet ovog rada je ispitivanje lipofilnosti novosintetisanih derivata cikloalkilspiro-5-hidantoina. Parametri lipofilnosti (RM0) za ispitivana jedinjenja dobijeni su primenom reversno fazne hromatografije na tankom sloju C-18 modifikovanog slikagela. Kao pokretne faze korišćene su dvokomponentne smeše vode i protičnih organskih rastvarača (metanola, etanola, n-propanola, i-propanola i t-butanola). Linearna zavisnost između RM vrednosti i zapreminskog udela organskog modifikatora u pokretnoj fazi, φ, omogućava izračunavanje RM0 ispitivanih jedinjenja. Uticaj supstituenata, kao modifikatora pokretne faze na RM0 vrednosti procenjen je primenom hemometrijskih metoda, hijerarhijske kalster analize (HCA) i analize glavnih komponenata (PCA). Ove metode omogućavaju grupisanje ispitivanih derivata spirohidantoina, kao i primenjenih pokretnih faza prema njihovoj polarnosti.
AB  - The subjects of this paper are newly synthesized derivatives of cycloalkylspiro-5-
hydantoins and the analysis of their lipophilicity. The parameters of lipophilicity (RM0) were
determined by reverse phase thin layer chromatography on C-18 modified silica gel. Mobile
phases were two-component mixtures of water and protic organic solvents (i.e. methanol,
ethanol, n-propanol, i-propanol and t-butanol). Linear relationship between RM values and
volume fraction of organic solvent, φ, allows calculation of RM0
for investigated compounds.
The effect of the substituents in the molecule as well as mobile phase modifier on RM0
value
was assessed using chemometric methods, hierarchical cluster analysis (HCA) and principal
component analysis (PCA). This allows clustering of spiro hydantoin derivatives as well as
applied mobile phases according to their polarity.
PB  - Beograd : Srpsko hemijsko društvo
C3  - Program i kratki izvodi radova / 53. savetovanje Srpskog hemijskog društva, Kragujevac, 10. i 11. jun 2016
T1  - Hemometrijska analiza parametara lipofilnosti novosintetisanih spirohidantoina koji su određeni na RP-TLC sa protičnim rastvaračima
T1  - Chemometric analysis of lipophilicity parameters of newly synthesized spiro hydantoin derivatives determined by RP-TLC and protic solvents
SP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6784
ER  - 

@conference{
author = "Tot, Jadranka A. and Tot, Kristina A. and Đaković-Sekulić, Tatjana Lj. and Lazić, Anita M. and Ušćumlić, Gordana S.",
year = "2016",
abstract = "Predmet ovog rada je ispitivanje lipofilnosti novosintetisanih derivata cikloalkilspiro-5-hidantoina. Parametri lipofilnosti (RM0) za ispitivana jedinjenja dobijeni su primenom reversno fazne hromatografije na tankom sloju C-18 modifikovanog slikagela. Kao pokretne faze korišćene su dvokomponentne smeše vode i protičnih organskih rastvarača (metanola, etanola, n-propanola, i-propanola i t-butanola). Linearna zavisnost između RM vrednosti i zapreminskog udela organskog modifikatora u pokretnoj fazi, φ, omogućava izračunavanje RM0 ispitivanih jedinjenja. Uticaj supstituenata, kao modifikatora pokretne faze na RM0 vrednosti procenjen je primenom hemometrijskih metoda, hijerarhijske kalster analize (HCA) i analize glavnih komponenata (PCA). Ove metode omogućavaju grupisanje ispitivanih derivata spirohidantoina, kao i primenjenih pokretnih faza prema njihovoj polarnosti., The subjects of this paper are newly synthesized derivatives of cycloalkylspiro-5-
hydantoins and the analysis of their lipophilicity. The parameters of lipophilicity (RM0) were
determined by reverse phase thin layer chromatography on C-18 modified silica gel. Mobile
phases were two-component mixtures of water and protic organic solvents (i.e. methanol,
ethanol, n-propanol, i-propanol and t-butanol). Linear relationship between RM values and
volume fraction of organic solvent, φ, allows calculation of RM0
for investigated compounds.
The effect of the substituents in the molecule as well as mobile phase modifier on RM0
value
was assessed using chemometric methods, hierarchical cluster analysis (HCA) and principal
component analysis (PCA). This allows clustering of spiro hydantoin derivatives as well as
applied mobile phases according to their polarity.",
publisher = "Beograd : Srpsko hemijsko društvo",
journal = "Program i kratki izvodi radova / 53. savetovanje Srpskog hemijskog društva, Kragujevac, 10. i 11. jun 2016",
title = "Hemometrijska analiza parametara lipofilnosti novosintetisanih spirohidantoina koji su određeni na RP-TLC sa protičnim rastvaračima, Chemometric analysis of lipophilicity parameters of newly synthesized spiro hydantoin derivatives determined by RP-TLC and protic solvents",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6784"
}

Tot, J. A., Tot, K. A., Đaković-Sekulić, T. Lj., Lazić, A. M.,& Ušćumlić, G. S.. (2016). Hemometrijska analiza parametara lipofilnosti novosintetisanih spirohidantoina koji su određeni na RP-TLC sa protičnim rastvaračima. in Program i kratki izvodi radova / 53. savetovanje Srpskog hemijskog društva, Kragujevac, 10. i 11. jun 2016
Beograd : Srpsko hemijsko društvo., 34.
https://hdl.handle.net/21.15107/rcub_technorep_6784

Tot JA, Tot KA, Đaković-Sekulić TL, Lazić AM, Ušćumlić GS. Hemometrijska analiza parametara lipofilnosti novosintetisanih spirohidantoina koji su određeni na RP-TLC sa protičnim rastvaračima. in Program i kratki izvodi radova / 53. savetovanje Srpskog hemijskog društva, Kragujevac, 10. i 11. jun 2016. 2016;:34.
https://hdl.handle.net/21.15107/rcub_technorep_6784 .

Tot, Jadranka A., Tot, Kristina A., Đaković-Sekulić, Tatjana Lj., Lazić, Anita M., Ušćumlić, Gordana S., "Hemometrijska analiza parametara lipofilnosti novosintetisanih spirohidantoina koji su određeni na RP-TLC sa protičnim rastvaračima" in Program i kratki izvodi radova / 53. savetovanje Srpskog hemijskog društva, Kragujevac, 10. i 11. jun 2016 (2016):34,
https://hdl.handle.net/21.15107/rcub_technorep_6784 .

TY  - JOUR
AU  - Đaković-Sekulić, Tatjana
AU  - Keleman, Svetlana
AU  - Tot, Kristina
AU  - Tot, Jadranka
AU  - Trišović, Nemanja
AU  - Ušćumlić, Gordana
PY  - 2016
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/3164
AB  - New synthesized compounds, particularly those with biological activity, are potential drug candidates. This article describes experimental studies performed to estimate lipophilicity parameters of new 3-(4-substituted benzyl)-5-phenylhydantoins. Lipophilicity, as one of the most important molecular characteristics for the activity, was determined using the reversed-phase liquid chromatography (RP-18 stationary phase and methanol-water mobile phase). Molecular structures were used to generate in silico data which were used to estimate pharmacokinetic properties of the investigated compounds. The results show that generally, the investigated compounds attain good bioavailability properties. A more detailed analysis shows that the presence of a nitro, methoxy and tert-butyl group in the molecule is indicated as unfavorable for the oral bioavailability of hydantoins. Multivariate exploratory analysis was used in order to visualize grouping patterns among molecular descriptors as well as among the investigated compounds. Molecular docking study performed for two hydantoins with the highest bioavailability scores shows high binding affinity to tyrosine kinase receptor IGF-1R. The results achieved can be useful as a template for future development and further derivation or modification to obtain more potent and selective antitumor agents.
T2  - Combinatorial Chemistry and High Throughput Screening
T1  - In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins
EP  - 443
IS  - 6
SP  - 437
VL  - 19
UR  - https://hdl.handle.net/21.15107/rcub_technorep_3164
ER  - 

@article{
author = "Đaković-Sekulić, Tatjana and Keleman, Svetlana and Tot, Kristina and Tot, Jadranka and Trišović, Nemanja and Ušćumlić, Gordana",
year = "2016",
abstract = "New synthesized compounds, particularly those with biological activity, are potential drug candidates. This article describes experimental studies performed to estimate lipophilicity parameters of new 3-(4-substituted benzyl)-5-phenylhydantoins. Lipophilicity, as one of the most important molecular characteristics for the activity, was determined using the reversed-phase liquid chromatography (RP-18 stationary phase and methanol-water mobile phase). Molecular structures were used to generate in silico data which were used to estimate pharmacokinetic properties of the investigated compounds. The results show that generally, the investigated compounds attain good bioavailability properties. A more detailed analysis shows that the presence of a nitro, methoxy and tert-butyl group in the molecule is indicated as unfavorable for the oral bioavailability of hydantoins. Multivariate exploratory analysis was used in order to visualize grouping patterns among molecular descriptors as well as among the investigated compounds. Molecular docking study performed for two hydantoins with the highest bioavailability scores shows high binding affinity to tyrosine kinase receptor IGF-1R. The results achieved can be useful as a template for future development and further derivation or modification to obtain more potent and selective antitumor agents.",
journal = "Combinatorial Chemistry and High Throughput Screening",
title = "In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins",
pages = "443-437",
number = "6",
volume = "19",
url = "https://hdl.handle.net/21.15107/rcub_technorep_3164"
}

Đaković-Sekulić, T., Keleman, S., Tot, K., Tot, J., Trišović, N.,& Ušćumlić, G.. (2016). In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins. in Combinatorial Chemistry and High Throughput Screening, 19(6), 437-443.
https://hdl.handle.net/21.15107/rcub_technorep_3164

Đaković-Sekulić T, Keleman S, Tot K, Tot J, Trišović N, Ušćumlić G. In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins. in Combinatorial Chemistry and High Throughput Screening. 2016;19(6):437-443.
https://hdl.handle.net/21.15107/rcub_technorep_3164 .

Đaković-Sekulić, Tatjana, Keleman, Svetlana, Tot, Kristina, Tot, Jadranka, Trišović, Nemanja, Ušćumlić, Gordana, "In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins" in Combinatorial Chemistry and High Throughput Screening, 19, no. 6 (2016):437-443,
https://hdl.handle.net/21.15107/rcub_technorep_3164 .

TY  - JOUR
AU  - Đaković-Sekulić, Tatjana
AU  - Vastag, Gyongyi
AU  - Tot, Kristina
AU  - Tot, Jadranka
AU  - Lazić, Anita
PY  - 2016
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/3364
AB  - Modeling properties of newly synthesized compounds is important for both understanding their activity and predicting their interactions. This paper describes the evaluation of the lipophilicity of the newly synthesized cycloalkylspiro-5-hydantoins by experimental and calculation methods. The chromatographic lipophilicity (R-M(0)) of the analyzed compounds was determined by reversed-phase liquid chromatographic system consisting of RP-18 stationary phase and methanol-water mobile phase. Correlation coefficients between R-M(0) values and the predicted log P were above 0.93, indicating a strong linear relationship between the variables. Multivariate data analysis applied in this study enabled the comparison of the lipophilicity and the structure of the investigated compounds using solely information obtained from thin-layer chromatography. Hierarchical clustering analysis (HCA) reveals a high similarity between R-M(0) and miLogP whereas squared log Ps such as ALOGP2 and MLOGP2 were distinct from R-M(0). HCA classifies the investigated compounds into three clusters according to lipophilicity. Principal component analysis (PCA) yields two principal components which explained  gt 99.19% total variance. The changes in the lipophilicity of the substituents attached in the molecule are reflected in the value of PCs. An increase in the lipophilicity of spiro substituent results in a decrease of values of both PC1 and PC2. The increase in the lipophilicity of R substituent decreases the value of PC1 and increases the value of PC2. The positive value of PC1 is typical for the compounds with the electron withdrawing groups such as CN, NO2, or OCH3.
PB  - Akademiai Kiado Zrt, Budapest
T2  - JPC-Journal of Planar Chromatography-Modern Tlc
T1  - Quantitative Structure-Retention Relationships Modeling and Multivariate Data Analysis of Lipophilicity Data of New Spirohydantoin Derivatives
EP  - 286
IS  - 4
SP  - 281
VL  - 29
DO  - 10.1556/1006.2016.29.4.6
ER  - 

@article{
author = "Đaković-Sekulić, Tatjana and Vastag, Gyongyi and Tot, Kristina and Tot, Jadranka and Lazić, Anita",
year = "2016",
abstract = "Modeling properties of newly synthesized compounds is important for both understanding their activity and predicting their interactions. This paper describes the evaluation of the lipophilicity of the newly synthesized cycloalkylspiro-5-hydantoins by experimental and calculation methods. The chromatographic lipophilicity (R-M(0)) of the analyzed compounds was determined by reversed-phase liquid chromatographic system consisting of RP-18 stationary phase and methanol-water mobile phase. Correlation coefficients between R-M(0) values and the predicted log P were above 0.93, indicating a strong linear relationship between the variables. Multivariate data analysis applied in this study enabled the comparison of the lipophilicity and the structure of the investigated compounds using solely information obtained from thin-layer chromatography. Hierarchical clustering analysis (HCA) reveals a high similarity between R-M(0) and miLogP whereas squared log Ps such as ALOGP2 and MLOGP2 were distinct from R-M(0). HCA classifies the investigated compounds into three clusters according to lipophilicity. Principal component analysis (PCA) yields two principal components which explained  gt 99.19% total variance. The changes in the lipophilicity of the substituents attached in the molecule are reflected in the value of PCs. An increase in the lipophilicity of spiro substituent results in a decrease of values of both PC1 and PC2. The increase in the lipophilicity of R substituent decreases the value of PC1 and increases the value of PC2. The positive value of PC1 is typical for the compounds with the electron withdrawing groups such as CN, NO2, or OCH3.",
publisher = "Akademiai Kiado Zrt, Budapest",
journal = "JPC-Journal of Planar Chromatography-Modern Tlc",
title = "Quantitative Structure-Retention Relationships Modeling and Multivariate Data Analysis of Lipophilicity Data of New Spirohydantoin Derivatives",
pages = "286-281",
number = "4",
volume = "29",
doi = "10.1556/1006.2016.29.4.6"
}

Đaković-Sekulić, T., Vastag, G., Tot, K., Tot, J.,& Lazić, A.. (2016). Quantitative Structure-Retention Relationships Modeling and Multivariate Data Analysis of Lipophilicity Data of New Spirohydantoin Derivatives. in JPC-Journal of Planar Chromatography-Modern Tlc
Akademiai Kiado Zrt, Budapest., 29(4), 281-286.
https://doi.org/10.1556/1006.2016.29.4.6

Đaković-Sekulić T, Vastag G, Tot K, Tot J, Lazić A. Quantitative Structure-Retention Relationships Modeling and Multivariate Data Analysis of Lipophilicity Data of New Spirohydantoin Derivatives. in JPC-Journal of Planar Chromatography-Modern Tlc. 2016;29(4):281-286.
doi:10.1556/1006.2016.29.4.6 .

Đaković-Sekulić, Tatjana, Vastag, Gyongyi, Tot, Kristina, Tot, Jadranka, Lazić, Anita, "Quantitative Structure-Retention Relationships Modeling and Multivariate Data Analysis of Lipophilicity Data of New Spirohydantoin Derivatives" in JPC-Journal of Planar Chromatography-Modern Tlc, 29, no. 4 (2016):281-286,
https://doi.org/10.1556/1006.2016.29.4.6 . .