Synthesis of the first spacer containing prodrug of a duocarmycin analogue and determination of its biological activity
2010 | journal article. A publication with affiliation to the University of Göttingen.
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Synthesis of the first spacer containing prodrug of a duocarmycin analogue and determination of its biological activity
Schuster, H. J.; Krewer, B.; von Hof, J. M.; Schmuck, K.; Schuberth, I.; Alves, F. & Tietze, L. F. (2010)
Organic & Biomolecular Chemistry, 8(8) pp. 1833-1842. DOI: https://doi.org/10.1039/b925070k
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Details
- Authors
- Schuster, Heiko J.; Krewer, Birgit; von Hof, J. Marian; Schmuck, Kianga; Schuberth, Ingrid; Alves, Frauke ; Tietze, Lutz Friedjan
- Abstract
- The synthesis of the first spacer containing, duocarmycin analogue prodrug 11 was realised, its biological properties evaluated and compared to its counterpart prodrug 2 without a spacer unit. The synthesis comprises the manufacture of the new acetylated derivatives 19 and 20b of two double spacer systems, their activation and coupling to the pharmacophoric seco-drug (+)-3. Unprecedented biological results were found as the new prodrug 11 showed a fairly low QIC(50) value of 20, but on the other hand a high stability and very low DNA alkylation efficiency. These findings indicate a changed cytostatic mode of action induced by the self-immolative spacer moiety which was employed.
- Issue Date
- 2010
- Status
- published
- Publisher
- Royal Soc Chemistry
- Journal
- Organic & Biomolecular Chemistry
- ISSN
- 1477-0520
