Details

Autor(en) / Beteiligte

• El Aissi, Radhia
• Chezal, Jean-Michel
• Tarrit, Sébastien
• Chavignon, Olivier
• Moreau, Emmanuel

Titel

Melanoma-targeted delivery system (part 1): Design, synthesis and evaluation of releasable disulfide drug by glutathione

Ist Teil von

• European journal of medicinal chemistry, 2015-08, Vol.101, p.668-680

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Here we describe the design and synthesis of a prodrug developed for pigmented melanoma therapy, consisting of a Melanin-Targeting Probe (MTP) conjugated to 5-iodo-2′-deoxyuridine (IUdR) with a reduction-sensitive pre-determined breaking point. Compared with the non-cleavable conjugate (17b), prodrug (17a) bearing a self-immolative disulfide linker achieved complete release of IUdR within 20 min in the presence of reducing agents such as DTT or glutathione. Analytical results also showed that prodrug (17a) was more sensitive than parent non-cleavable conjugate (17b) for a concentration range of glutathione similar to that found in the intracellular compartment of tumours. IUdR release was performed after treatment of disulfide prodrug IUdR–SS–MTP (17a) by disulfide reduction conditions (DTT or glutathione). [Display omitted] •(17a) enabled the complete release of IUdR within 20 min under reductive conditions.•Release of IUdR was also confirmed by HPLC analysis under reductive conditions.•Our versatile synthetic approach can be applied to various cytotoxic agents.