Structure-Retention Relationship Study of HPLC Data of Antiepileptic Hydantoin Analogues
Abstract
In the study, 18 antiepileptic hydantoin analogues were investigated by means of reversed-phase HPLC on C-18 stationary phase and eluent acetonitrile-water. Quantitative structure-retention relationship (QSRR) study has been applied in order to understand factors that affect the retention which is closely correlated to the activity (ED50 values). To overview the compounds for similarities and dissimilarities principal component analysis (PCA) has been applied. Six multiple linear regression models based on the most relevant descriptors were developed. Descriptors for MLR were selected according to variable importance calculated by partial least squares (PLS) analysis. Besides ALOGP the most important is aromatic ratio for mobile phases with more than 45% of acetonitrile, as well as electrotopological states when the % of acetonitrile is less than 40%. High agreement between experimental and predicted retention, obtained in the validation procedure, indicated the good quality of the der...ived QSRR models. For individual linear models, cross-validation squared correlation coefficients (Q(2)) ranging from 0.697 to 0.837 were obtained. The residual values (difference between observed and calculated) agreed well within experimental error. Additionally, models were compared in terms of the smallest residual value by recently developed method of ranking based on the sum of ranking differences (SRD).
Keywords:
Antiepileptic hydantoin analogues / quantitative structure-retention relationship (QSRR) / liquid chromatography / activity / principal component analysis (PCA) / multiple linear regression (MLR) / sum of ranking differences (SRD)Source:
Current Computer-Aided Drug Design, 2012, 8, 1, 3-9Publisher:
- Bentham Science Publ Ltd, Sharjah
Funding / projects:
- Study of the Synthesis, Structure and Activity of Natural and Synthetic Organic Compounds (RS-MESTD-Basic Research (BR or ON)-172013)
DOI: 10.2174/157340912799218525
ISSN: 1573-4099
PubMed: 21692743
WoS: 000300634300002
Scopus: 2-s2.0-84857696276
Institution/Community
Tehnološko-metalurški fakultetTY - JOUR AU - Đaković-Sekulić, Tatjana AU - Mandić, Anamarija AU - Trišović, Nemanja AU - Ušćumlić, Gordana PY - 2012 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2231 AB - In the study, 18 antiepileptic hydantoin analogues were investigated by means of reversed-phase HPLC on C-18 stationary phase and eluent acetonitrile-water. Quantitative structure-retention relationship (QSRR) study has been applied in order to understand factors that affect the retention which is closely correlated to the activity (ED50 values). To overview the compounds for similarities and dissimilarities principal component analysis (PCA) has been applied. Six multiple linear regression models based on the most relevant descriptors were developed. Descriptors for MLR were selected according to variable importance calculated by partial least squares (PLS) analysis. Besides ALOGP the most important is aromatic ratio for mobile phases with more than 45% of acetonitrile, as well as electrotopological states when the % of acetonitrile is less than 40%. High agreement between experimental and predicted retention, obtained in the validation procedure, indicated the good quality of the derived QSRR models. For individual linear models, cross-validation squared correlation coefficients (Q(2)) ranging from 0.697 to 0.837 were obtained. The residual values (difference between observed and calculated) agreed well within experimental error. Additionally, models were compared in terms of the smallest residual value by recently developed method of ranking based on the sum of ranking differences (SRD). PB - Bentham Science Publ Ltd, Sharjah T2 - Current Computer-Aided Drug Design T1 - Structure-Retention Relationship Study of HPLC Data of Antiepileptic Hydantoin Analogues EP - 9 IS - 1 SP - 3 VL - 8 DO - 10.2174/157340912799218525 ER -
@article{ author = "Đaković-Sekulić, Tatjana and Mandić, Anamarija and Trišović, Nemanja and Ušćumlić, Gordana", year = "2012", abstract = "In the study, 18 antiepileptic hydantoin analogues were investigated by means of reversed-phase HPLC on C-18 stationary phase and eluent acetonitrile-water. Quantitative structure-retention relationship (QSRR) study has been applied in order to understand factors that affect the retention which is closely correlated to the activity (ED50 values). To overview the compounds for similarities and dissimilarities principal component analysis (PCA) has been applied. Six multiple linear regression models based on the most relevant descriptors were developed. Descriptors for MLR were selected according to variable importance calculated by partial least squares (PLS) analysis. Besides ALOGP the most important is aromatic ratio for mobile phases with more than 45% of acetonitrile, as well as electrotopological states when the % of acetonitrile is less than 40%. High agreement between experimental and predicted retention, obtained in the validation procedure, indicated the good quality of the derived QSRR models. For individual linear models, cross-validation squared correlation coefficients (Q(2)) ranging from 0.697 to 0.837 were obtained. The residual values (difference between observed and calculated) agreed well within experimental error. Additionally, models were compared in terms of the smallest residual value by recently developed method of ranking based on the sum of ranking differences (SRD).", publisher = "Bentham Science Publ Ltd, Sharjah", journal = "Current Computer-Aided Drug Design", title = "Structure-Retention Relationship Study of HPLC Data of Antiepileptic Hydantoin Analogues", pages = "9-3", number = "1", volume = "8", doi = "10.2174/157340912799218525" }
Đaković-Sekulić, T., Mandić, A., Trišović, N.,& Ušćumlić, G.. (2012). Structure-Retention Relationship Study of HPLC Data of Antiepileptic Hydantoin Analogues. in Current Computer-Aided Drug Design Bentham Science Publ Ltd, Sharjah., 8(1), 3-9. https://doi.org/10.2174/157340912799218525
Đaković-Sekulić T, Mandić A, Trišović N, Ušćumlić G. Structure-Retention Relationship Study of HPLC Data of Antiepileptic Hydantoin Analogues. in Current Computer-Aided Drug Design. 2012;8(1):3-9. doi:10.2174/157340912799218525 .
Đaković-Sekulić, Tatjana, Mandić, Anamarija, Trišović, Nemanja, Ušćumlić, Gordana, "Structure-Retention Relationship Study of HPLC Data of Antiepileptic Hydantoin Analogues" in Current Computer-Aided Drug Design, 8, no. 1 (2012):3-9, https://doi.org/10.2174/157340912799218525 . .