Chromatographic retention parameters in correlation analysis with in silico biological descriptors of a novel series of N-phenyl-3-methyl succinimide derivatives
Abstract
Reversed-phase thin-layer chromatographic (RP TLC) retention coefficients for a newly designed series of N-phenyl-3-methyl succinimide derivatives, of a rationally expected anticonvusant activity, were determined as parameters of their lipophilicity. Basic pharmacokinetic descriptors of the agents were calculated in silico with the use of the established medicinal chemistry/drug design software. Highly significant, predictive relationships were found between the chromatographic retention constants and the bioactivity descriptors, which are assumed to account for drug absorption, distribution, elimination and toxicity (ADMETox) in humans. Among the agents investigated, the compounds with halogen substituent (Compounds nos. 9-13 in Fig. 1), were identified as the best drug candidates, because of their predicted proper pharmacokinetics, and have been selected for further research and development studies on new antiepileptic drugs. At the same time, among the congeners studied these can be... indicated, which should not be rationally subjected to bioactivity tests.
Keywords:
Succinmides / Reversed-phase thin layer chromatography / In silico ADMETox determination / QSRR/QSAR - quantitative structure-retention/activity relationships / Rational drug designSource:
Journal of Pharmaceutical and Biomedical Analysis, 2013, 72, 65-73Publisher:
- Elsevier, Amsterdam
Funding / projects:
- Study of the Synthesis, Structure and Activity of Natural and Synthetic Organic Compounds (RS-172013)
- Ministry of Science and Higher Education of PolandMinistry of Science and Higher Education, Poland [N405630038]
DOI: 10.1016/j.jpba.2012.09.006
ISSN: 0731-7085
PubMed: 23146228
WoS: 000311819100009
Scopus: 2-s2.0-84869015092
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Institution/Community
Poljoprivredni fakultetTY - JOUR AU - Perisić-Janjić, Nada AU - Kaliszan, Roman AU - Milošević, Nataša AU - Ušćumlić, Gordana AU - Banjac, Nebojša PY - 2013 UR - http://aspace.agrif.bg.ac.rs/handle/123456789/3313 AB - Reversed-phase thin-layer chromatographic (RP TLC) retention coefficients for a newly designed series of N-phenyl-3-methyl succinimide derivatives, of a rationally expected anticonvusant activity, were determined as parameters of their lipophilicity. Basic pharmacokinetic descriptors of the agents were calculated in silico with the use of the established medicinal chemistry/drug design software. Highly significant, predictive relationships were found between the chromatographic retention constants and the bioactivity descriptors, which are assumed to account for drug absorption, distribution, elimination and toxicity (ADMETox) in humans. Among the agents investigated, the compounds with halogen substituent (Compounds nos. 9-13 in Fig. 1), were identified as the best drug candidates, because of their predicted proper pharmacokinetics, and have been selected for further research and development studies on new antiepileptic drugs. At the same time, among the congeners studied these can be indicated, which should not be rationally subjected to bioactivity tests. PB - Elsevier, Amsterdam T2 - Journal of Pharmaceutical and Biomedical Analysis T1 - Chromatographic retention parameters in correlation analysis with in silico biological descriptors of a novel series of N-phenyl-3-methyl succinimide derivatives EP - 73 SP - 65 VL - 72 DO - 10.1016/j.jpba.2012.09.006 ER -
@article{ author = "Perisić-Janjić, Nada and Kaliszan, Roman and Milošević, Nataša and Ušćumlić, Gordana and Banjac, Nebojša", year = "2013", abstract = "Reversed-phase thin-layer chromatographic (RP TLC) retention coefficients for a newly designed series of N-phenyl-3-methyl succinimide derivatives, of a rationally expected anticonvusant activity, were determined as parameters of their lipophilicity. Basic pharmacokinetic descriptors of the agents were calculated in silico with the use of the established medicinal chemistry/drug design software. Highly significant, predictive relationships were found between the chromatographic retention constants and the bioactivity descriptors, which are assumed to account for drug absorption, distribution, elimination and toxicity (ADMETox) in humans. Among the agents investigated, the compounds with halogen substituent (Compounds nos. 9-13 in Fig. 1), were identified as the best drug candidates, because of their predicted proper pharmacokinetics, and have been selected for further research and development studies on new antiepileptic drugs. At the same time, among the congeners studied these can be indicated, which should not be rationally subjected to bioactivity tests.", publisher = "Elsevier, Amsterdam", journal = "Journal of Pharmaceutical and Biomedical Analysis", title = "Chromatographic retention parameters in correlation analysis with in silico biological descriptors of a novel series of N-phenyl-3-methyl succinimide derivatives", pages = "73-65", volume = "72", doi = "10.1016/j.jpba.2012.09.006" }
Perisić-Janjić, N., Kaliszan, R., Milošević, N., Ušćumlić, G.,& Banjac, N.. (2013). Chromatographic retention parameters in correlation analysis with in silico biological descriptors of a novel series of N-phenyl-3-methyl succinimide derivatives. in Journal of Pharmaceutical and Biomedical Analysis Elsevier, Amsterdam., 72, 65-73. https://doi.org/10.1016/j.jpba.2012.09.006
Perisić-Janjić N, Kaliszan R, Milošević N, Ušćumlić G, Banjac N. Chromatographic retention parameters in correlation analysis with in silico biological descriptors of a novel series of N-phenyl-3-methyl succinimide derivatives. in Journal of Pharmaceutical and Biomedical Analysis. 2013;72:65-73. doi:10.1016/j.jpba.2012.09.006 .
Perisić-Janjić, Nada, Kaliszan, Roman, Milošević, Nataša, Ušćumlić, Gordana, Banjac, Nebojša, "Chromatographic retention parameters in correlation analysis with in silico biological descriptors of a novel series of N-phenyl-3-methyl succinimide derivatives" in Journal of Pharmaceutical and Biomedical Analysis, 72 (2013):65-73, https://doi.org/10.1016/j.jpba.2012.09.006 . .