Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(Duocarmycin). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of Bath

1. Twum, Elvis Asare. Development of prodrugs to deliver super-potent drugs to prostate tumours.

Degree: PhD, 2013, University of Bath

Conventional treatments for prostate cancer have significant limitations making it difficult to control the disease. Cyclopropabenzindoles (CBI) are more biologically potent, stable and synthetically accessible analogues of cyclopropapyrroloindole (CPI) anti-tumour antibiotics, such as duocarmycin-SA and CC1065. A polymeric prodrug carrying a CBI drug attached to the polymeric backbone through a PSA cleavable linker peptide has two modes of selectivity: activation by PSA and the EPR effect. To synthesise a 5-amino-seco-CBI analogue, 2,4-dinitronaphthalen- 1-ol gave di-Boc-1-iodonaphthalene-2,4-diamine in five steps (triflation, SNAr displacement with iodide, reduction (loss of iodine), protection and restoration of the iodine. For the amino-seco-CBI, it was important to discriminate between N2 and N4. Acidic removal of the Boc-group(s) resulted in deiodination. NMR investigations showed an unexpected Wheland-like cationic intermediate. N3 of naphthalene-1,3-diamine was selectively trifluoroacetylated and N1 was masked with Boc. Electrophilic iodination gave an orthogonally protected 1-iodonaphthalene-2,4-diamine. Allylation at the trifluoroacetamide was followed by free radical cyclisation with TEMPO trap. Removal of the trifluoroacetyl group allowed coupling to 5-(2-(dimethylamino)ethoxy)-1H-indole-2-carboxylic acid. Reductive removal of 2,2,6,6-tetramethylpiperidine, substitution of the exposed hydroxy group with chloride and removal of the Boc-group gave the amino-seco-CBI drug, 5-amino-1-chloromethyl-3-(5-(2-dimethylaminoethoxy)indole-2-carbonyl)-2,3-dihydro-1H-benz[e]indole. A DNA-melting assay confirmed that it binds very strongly to dsDNA causing a 13 deg. C increase in melting temperature. The drug was a highly potent cytotoxin in vitro, with IC50 = 18 nM against LNCaP prostate cancer cells. The polymeric prodrug system involved the synthesis of the pentapeptide SSKLQ. The amide side chain of glutamine can be masked as the nitrile and this can be quantitatively hydrated to the γ-carboxamide of L-Gln with hydroperoxide. The pentapeptide was coupled to 4-methoxynaphthalen-1-amine and to poly(ethylene glycol) as a model polymeric prodrug system. Efficient release of the model drug from the polymeric prodrug by PSA will allow this polymeric prodrug system to be adopted for the synthesised amino-seco-CBI drug.

Subjects/Keywords: 616.99463061; duocarmycin; CC-1065; cyclopropabenzindole; cyclopropapyrroloindole; ant-tumour; cancer; prostate; peptide; prodrugs; EPR; polymer

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Twum, E. A. (2013). Development of prodrugs to deliver super-potent drugs to prostate tumours. (Doctoral Dissertation). University of Bath. Retrieved from https://researchportal.bath.ac.uk/en/studentthesis/development-of-prodrugs-to-deliver-superpotent-drugs-to-prostate-tumors(8765e781-5ef8-4bae-8121-37196ac38de7).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608329

Chicago Manual of Style (16th Edition):

Twum, Elvis Asare. “Development of prodrugs to deliver super-potent drugs to prostate tumours.” 2013. Doctoral Dissertation, University of Bath. Accessed April 17, 2021. https://researchportal.bath.ac.uk/en/studentthesis/development-of-prodrugs-to-deliver-superpotent-drugs-to-prostate-tumors(8765e781-5ef8-4bae-8121-37196ac38de7).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608329.

MLA Handbook (7th Edition):

Twum, Elvis Asare. “Development of prodrugs to deliver super-potent drugs to prostate tumours.” 2013. Web. 17 Apr 2021.

Vancouver:

Twum EA. Development of prodrugs to deliver super-potent drugs to prostate tumours. [Internet] [Doctoral dissertation]. University of Bath; 2013. [cited 2021 Apr 17]. Available from: https://researchportal.bath.ac.uk/en/studentthesis/development-of-prodrugs-to-deliver-superpotent-drugs-to-prostate-tumors(8765e781-5ef8-4bae-8121-37196ac38de7).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608329.

Council of Science Editors:

Twum EA. Development of prodrugs to deliver super-potent drugs to prostate tumours. [Doctoral Dissertation]. University of Bath; 2013. Available from: https://researchportal.bath.ac.uk/en/studentthesis/development-of-prodrugs-to-deliver-superpotent-drugs-to-prostate-tumors(8765e781-5ef8-4bae-8121-37196ac38de7).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608329


University of Bradford

2. Presa, Daniella F. S. Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer : probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors.

Degree: PhD, 2018, University of Bradford

Subjects/Keywords: Cytochrome P450 (CYP); CYP1A1; CYP1B1; CYP2W1; Head and Neck Cancer (HNC); Duocarmycin; Prodrug; Bioprecursor; DNA damage; Therapeutic intervention

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Presa, D. F. S. (2018). Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer : probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors. (Doctoral Dissertation). University of Bradford. Retrieved from http://hdl.handle.net/10454/18171

Chicago Manual of Style (16th Edition):

Presa, Daniella F S. “Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer : probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors.” 2018. Doctoral Dissertation, University of Bradford. Accessed April 17, 2021. http://hdl.handle.net/10454/18171.

MLA Handbook (7th Edition):

Presa, Daniella F S. “Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer : probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors.” 2018. Web. 17 Apr 2021.

Vancouver:

Presa DFS. Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer : probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors. [Internet] [Doctoral dissertation]. University of Bradford; 2018. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10454/18171.

Council of Science Editors:

Presa DFS. Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer : probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors. [Doctoral Dissertation]. University of Bradford; 2018. Available from: http://hdl.handle.net/10454/18171

.