Synthesis and pharmacological evaluation of a new targeted drug carrier system: β-Cyclodextrin coupled to oxytocin

[en] β-Cyclodextrin (β-CD) was monofunctionalized into its carboxylic derivative and then conjugated to the N-side of oxytocin (OT), a nonapeptide involved in human behavior and myometrium contraction. On isolated rat myometrium, this conjugate (β-CD-OT) partly preserves the contracting activity of OT (EC50 = 0.40 μM vs 1.7 nM). Moreover, the contraction induced frequency is also lowered by β-CD-OT. This novel hydrophilic targeted carrier could form a host–guest complex with prostaglandins and their derivatives used as labor inducers or with anticancer drugs used in cervix and endometrial cancer. This strategy can improve the solubility, the stability, and/or the biological activity of these drugs as well as reducing their side-effects.

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Bertolla, C; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique

Rolin, S

Evrard, Brigitte

Pochet, L

Masereel, B

Language :

English

Title :

Synthesis and pharmacological evaluation of a new targeted drug carrier system: β-Cyclodextrin coupled to oxytocin

Publication date :

2008

Journal title :

Bioorganic and Medicinal Chemistry Letters

ISSN :

0960-894X

eISSN :

1464-3405

Publisher :

Elsevier, United Kingdom

Volume :

Pages :

1855-1858

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 28 April 2010

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Bibliography

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Mono-6-deoxy-6-carboxy-β-cyclodextrin (4). Bromine (4 mL; 0.90 mmol) was added to a solution of 6-deoxy-6-formyl-β-cyclodextrin (3, 1.02 g; 0.90 mmol) in 0.1 M phosphate buffer (10 mL; pH 6.0). The solution was stirred for 5 days at room temperature in the dark. Then, excess of bromine was extracted by diethyl ether (4 × 20 mL). The aqueous phase was added to acetone (600 mL), and the formed precipitate was collected and purified by preparative LC/MS according to the above described procedure to give 0.21 g (yield = 20%) of the title compound 4. 1H NMR (400 MHz, DMSO-d6) δ 3.37-3.74 (overlap with D2O, 40 H), 3.83 (d, 1H), 4.38-4.45 (m, 6H), 4.73-4.97 (m, 7H); 5.63-5.75 (m, 14H); m/z 1150.1 [M+H]+, 171.2 [M+Na]+. Anal. Calcd for C42H68O36·4H2O: C, 41.31; H, 6.23. Found: C, 41.55; H, 6.11.
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