Chromatographic lipophilicity and pharmacokinetic behavior of some newly synthesized styryl lactone stereoisomers
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Faculty of Technology, Novi Sad
2017-01-01
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| Series: | Acta Periodica Technologica |
| Subjects: | |
| Online Access: | http://www.doiserbia.nb.rs/img/doi/1450-7188/2017/1450-71881748197L.pdf |
| Summary: | 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] |
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| ISSN: | 1450-7188 2406-095X |