Chromatographic lipophilicity and pharmacokinetic behavior of some newly synthesized styryl lactone stereoisomers
| Autor: | Lоnčаr Dаvоr М., Мilоšеvić Nаtаšа P., Vitas Jasmina S., Karadžić Milica Ž., Jevrić Lidija R., Benedeković Goran |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Acta Periodica Technologica, Vol 2017, Iss 48, Pp 197-209 (2017) |
| Druh dokumentu: | article |
| ISSN: | 1450-7188 2406-095X |
| DOI: | 10.2298/APT1748197L |
| Popis: | The RP-HPLC retention constants of several newly synthesized cytotoxic styryl lactone stereoisomers were determined as parameters of their lipophilicity. Stereochemistry of the compounds has an effect on the retention behavior of only tricyclic isomers. For them, the difference in retention and chromatographic lipophilic parameters are significant. The chromatographic lipophilic parameters of all compounds were correlated with a fourteen computer calculated lipophilic parameters, log P, and pharmacokinetic parameters. Significant linear correlations (R2 adj>0.90) were obtained between MLog P and affinity for plasma proteins binding. The correrelations for the other pharmacokinetic parameters were improved by introducing some more molecular descriptors. Multiple linear regression analysis suggested that the volume of distribution depended on the lipopholicity and Ka HSA (HSA-human serum albumin) and the absorption through membrane and permeability in the jejunum depend on the lipophilicity and hydrogen bond donors. The tested compounds showed a potent to moderate cytotoxic activity toward several human cancer cells and poor permeation through the blood brain barrier. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. OI 1612036] |
| Databáze: | Directory of Open Access Journals |
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