Solubilisation and cytotoxicity of albendazole encapsulated in cucurbit[n]uril.
The aqueous solubilities of albendazole encapsulated in cucurbit[6, 7 and 8]urils (Q[6], Q[7] and Q[8]) have been determined by (1)H NMR spectroscopy, and the effect of encapsulation on their cytotoxicities evaluated. Encapsulation in Q[6] and Q[7] increased the aqueous solubility of albendazole by 2000-fold, from 3 microM to 6 mM at pH 6.6, while Q[8]-encapsulation increased the solubility to over 2 mM. Encapsulation in Q[7] and Q[8] induced significant upfield shifts for the albendazole propyl and benzimidazole resonances, compared to those observed for Q[6]-binding and what would normally be expected for the respective functional groups. The upfield shifts indicate that the albendazole propyl and benzimidazole protons are located within the Q[7] and Q[8] cavity upon encapsulation. Alternatively, encapsulation in Q[6] only induced a large upfield shift for the albendazole carbamate methyl resonance, indicating that the drug associates with Q[6] at its portals, with only the carbamate group within the cavity. Simple molecular models based on the observed relative changes in chemical shift could be constructed that were consistent with the conclusions from the NMR experiments. Cytotoxicity assays against human colorectal cells (HT-29), human ovarian cancer cells (1A9) and the human T-cell acute lymphoblastic leukaemia cells (CEM) indicated that encapsulation in Q[7] did not significantly reduce the in vitro anti-cancer activity of albendazole.
Zhao
Yunjie
Y
School of Physical, Environmental and Mathematical Sciences, University College, University of New South Wales, Australian Defence Force Academy, Northcott Drive, Campbell, ACT 2600, Australia.
Buck
Damian P
DP
Morris
David L
DL
Pourgholami
Mohammad H
MH
Day
Anthony I
AI
Collins
J Grant
JG
D015766:Albendazole / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D012995:Solubility
D000970:Antineoplastic Agents; D007093:Imidazoles; D015766:Albendazole