Tools
Tools
Searcey, Mark 
ORCID: https://orcid.org/0000-0003-2273-8949
(2002)
Duocarmycins - Natures prodrugs?
Current Pharmaceutical Design, 8 (15).
pp. 1375-1389.
ISSN 1381-6128
Abstract
The duocarmycins and (+)-CC-1065 are amongst the most potent antitumour antibiotics discovered to date and yet have not progressed into the clinic. The natural products are extremely stable to nucleophilic attack until bound to their DNA target and are not substrates for any other biological nucleophile. The mechanism for this target activation of the duocarmycins is discussed with relation to both an acid-catalyzed activation and a binding-induced conformational change leading to ground state destabilization. It is suggested that targeting of the duocarmycins to their site of action in a tumour may be more important than introducing systemically-activated prodrugs as the natural product itself can be considered to be a type of prodrug, activated only on binding to its targets. Methods that have been used to target CC-1065 and the duocarmycins are reviewed as well as efforts towards systemically activated prodrugs. A simple analysis of the approaches that could be taken to vary the structure for targeting is suggested.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | cc-1065,functional,double-stranded dna,anti-tumor agent,noncovalent binding selectivity,analogs,left-hand subunit,dna-sequence specificity,groove alkylating-agents,antitumor antibiotic,biological-activity,seco-cbi-tmi |
| 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: | 13 Jun 2011 14:32 |
| Last Modified: | 24 Sep 2024 10:19 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/32129 |
| DOI: | 10.2174/1381612023394539 |
Actions (login required)
 |
View Item |