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ToolsHamilton, Chris J., Saravanamuthu, Ahilan, Poupat, Christiane, Fairlamb, Alan H. and Eggleston, Ian M. (2006) Time-dependent inhibitors of trypanothione reductase: Analogues of the spermidine alkaloid lunarine and related natural products. Bioorganic & Medicinal Chemistry, 14 (7). pp. 2266-2278. ISSN 0968-0896
Full text not available from this repository.Abstract
The macrocyclic spermidine alkaloid lunarine 1 from Lunaria biennis is a competitive, time-dependent inhibitor of the protozoan oxidoreductase trypanothione reductase (TryR), a promising target in drug design against tropical parasitic diseases. Various molecules related to I and the alkaloid itself have been synthesized in racemic form and evaluated against TryR in order to determine the key features of I that are associated with time-dependent inhibition. Kinetic data are consistent with an inactivation mechanism involving a conjugate addition of an active site cysteine residue onto the C-24-C-25 double bond of the tricyclic nucleus of 1. Comparison of data for synthetic (+/-)-1, the natural product, and other derivatives 7-10 from L. biennis confirms the importance of the unique structure of the tricyclic core as a motif for inhibitor design and reveals that the non-natural enantiomer may be a more suitable scaffold upon which thiophilic groups may be presented. (c) 2005 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | disulfide reductase,conjugate addition,time-dependent inhibitors,natural products |
| Faculty \ School: | Faculty of Science > School of Pharmacy (former - to 2024) |
| UEA Research Groups: | Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021) Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017) |
| Depositing User: | Rachel Smith |
| Date Deposited: | 17 May 2011 15:47 |
| Last Modified: | 24 Sep 2024 09:49 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/30704 |
| DOI: | 10.1016/j.bmc.2005.11.004 |
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