72072-06-1Relevant articles and documents
Development of a Prodrug of Camptothecin for Enhanced Treatment of Glioblastoma Multiforme
Checa-Chavarria, Elisa,Rivero-Buceta, Eva,Sanchez Martos, Miguel Angel,Martinez Navarrete, Gema,Soto-Sánchez, Cristina,Botella, Pablo,Fernández, Eduardo
, p. 1558 - 1572 (2021)
A novel therapeutic approach for glioblastoma multiforme (GBM) therapy has been carried out through in vitro and in vivo testing by using the prodrug camptothecin-20-O-(5-aminolevulinate) (CPT-ALA). The incorporation of ALA to CPT may promote uptake of the cytotoxic molecule by glioblastoma cells where the heme synthesis pathway is active, improving the therapeutic action and reducing the side effects over healthy tissue. The antitumor properties of CPT-ALA have been tested on different GBM cell lines (U87, U251, and C6) as well as in an orthotopic GBM model in rat, where potential toxicity in central nervous system cells was analyzed. In vitro results indicated no significant differences in the cytotoxic effect over the different GBM cell lines for CPT and CPT-ALA, albeit cell mortality induced by CPT over normal cell lines was significantly higher than CPT-ALA. Moreover, intracranial GBM in rat was significantly reduced (30% volume) with 2 weeks of CPT-ALA treatment with no significant side effects or alterations to the well-being of the animals tested. 5-ALA moiety enhances CPT diffusion into tumors due to solubility improvement and its metabolic-based targeting, increasing the CPT cytotoxic effect on malignant cells while reducing CPT diffusion to other proliferative healthy tissue. We demonstrate that CPT-ALA blocks proliferation of GBM cells, reducing the infiltrative capacity of GBM and promoting the success of surgical removal, which improves life expectancy by reducing tumor recurrence.
Peptide-targeted dendrimeric prodrugs of 5-aminolevulinic acid: A novel approach towards enhanced accumulation of protoporphyrin IX for photodynamic therapy
Tewari,Dondi,Yaghini,Pourzand,MacRobert,Eggleston
supporting information, (2021/02/26)
Photodynamic therapy (PDT) is a promising approach for the targeted treatment of cancer and various other human disorders. An effective, clinically approved approach in PDT involves the administration of 5-aminolevulinic acid (ALA) to generate elevated levels of the natural photosensitiser protoporphyrin IX (PpIX). The development of prodrugs of ALA is of considerable interest as a means to enhance the efficiency and cell selectivity of PpIX accumulation for PDT applications. In this work a novel peptide-targeted dendrimeric prodrug of 5-aminolevulinic acid (ALA) 13 was synthesised which displays nine copies of ALA on a core structure that is linked to a homing peptide for targeted delivery to a specific cancer cell type. The synthesis was accomplished effectively via a flexible, modular solid phase and solution phase route, using a combination of solid phase peptide synthesis and copper-catalysed azide-alkyne cycloaddition chemistry. The prodrug system shows a sustained and enhanced production of protoporphyrin IX (PpIX) in the MDA-MB-231 cell line that over-expresses the epidernal growth factor receptor (EGFR+) in comparison to equimolar ALA and the corresponding non-targeted ALA dendrimer (nine copies of ALA). This study provides a proof of concept for the development of a new generation of prodrugs for ALA-based photodynamic therapy that can deliver an enhanced ALA payload to specific tissue types.
Synthesis method of 5-aminolevulinic acid hydrochloride
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, (2019/04/26)
The invention relates to a synthesis method of 5-aminolevulinic acid hydrochloride (5-ALA), furfuryl amine (2-furylamine) is used as an initial raw material, and the target product is synthesized through four steps of amino protection, oxidation reaction, reduction reaction and hydrolysis decarboxylation. Reagents used in the synthesis method are low in price, easy to obtain, and environment-friendly and the operation is simple.
