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Investigations into neuroprotectivity, stability, and water solubility of 7‐ O ‐cinnamoylsilibinin, its hemisuccinate and dehydro derivatives
Author(s) -
Schramm Simon,
Gunesch Sandra,
Lang Florian,
Saedtler Marco,
Meinel Lorenz,
Högger Petra,
Decker Michael
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800206
Subject(s) - neuroprotection , chemistry , solubility , stereochemistry , organic chemistry , pharmacology , medicine
Derivatives of the recently described potent neuroprotective 7‐ O ‐cinnamoylsilibinin ester were prepared: its hemisuccinate to improve water solubility and the dehydrosilibinin ester that was shown to form in assay media to investigate its role in overall neuroprotective effects. 7‐ O ‐Cinnamoyl‐2,3‐dehydrosilibinin is less neuroprotective than 7‐ O ‐cinnamoylsilibinin in a murine hippocampal cell line (HT‐22) and we conclude that the dehydrosilibinin derivatives are not the actual carriers of neuroprotective properties, at least in the assay applied. Solubility of the test compounds was determined in shake‐flask experiments and the ester's solubility was greatly improved by introduction of a hemisuccinate at the 23‐position of silibinin. Time–stability curves in assay media were recorded. The hemisuccinate ester did not act as a prodrug to release 7‐ O ‐cinnamoylsilibinin but is the second ester bond to be cleaved. Nevertheless, it still exhibits significant neuroprotection. Therefore, its greatly increased solubility might effectively counterbalance lower in vitro neuroprotection.