A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins
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 relationshi...p between the variables. Multivariate data analysis enabled the comparison of the chemical structures, lipophilicity, pharmacokinetic predictors and toxicity of the investigated compounds.
Keywords:
Bioactivity and toxicity / chromatographic lipophilicity / cycloalkanespiro-5-hydantoins / multivariate methodsSource:
Journal of Liquid Chromatography & Related Technologies, 2020, 43, 19-20, 925-933Publisher:
- Taylor & Francis Inc, Philadelphia
Funding / projects:
DOI: 10.1080/10826076.2020.1856137
ISSN: 1082-6076
WoS: 000596979600001
Scopus: 2-s2.0-85097427789
Institution/Community
Inovacioni centarTY - 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 . .