Novel Bioconjugates of Aminolevulinic Acid with Vitamins

Abstract

5-Aminolevulinic acid (ALA) and derivatives thereof have been successfully used in photodynamic cancer therapy (PDT). The synthesis of novel bioconjugates combining ALA with two lipophilic and one hydrophilic vitamins is reported. The new bioconjugates allow studying the potential synergies between the two components in PDT. The synthetic methodology is robust giving the bioconjugates in good to satisfactory yield.

New Hydrophilic/Lipophilic Tetra-α-(4-carboxyphenoxy) Phthalocyanine Zinc-Mediated Photodynamic Therapy Inhibits the Proliferation of Human Hepatocellular Carcinoma Bel-7402 Cells by Triggering Apoptosis and Arresting Cell Cycle

“…At present, only a few porphyrin photosensitisers (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin) are approved for the treatment of cancer in humans. Although these photosensitisers have demonstrated a wider spectrum of antitumor effects, they have various deficiencies that spur the development of better photosensitiser candidates [4,5]. As a result of the desirable electronic absorption and photophysical properties, phthalocyanines, containing a planar macrocycle with an 18 π-electron system, are one of the most potential photosensitiser candidates [6,7].…”

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

“…The connection of 8 to 4 proceeded under standard coupling conditions (DCC, DMAP) [17] affording a water-soluble compound. The 1 H NMR spectrum of the product verified the presence of peaks arising both from 8 chain and 4 components, while the relative broadness of the signals indicated incomplete/random substitution, allowing, however, the assignment of peaks via the HSQC-edited spectrum (Supporting Information File 1, Figure S3).…”

Chemical approaches for the enhancement of 5-aminolevulinic acid-based photodynamic therapy and photodiagnosis

“…The esterification of ALA with various vitamins, monosaccharides and nucleoside derivatives has been explored both with a view to tailoring the physical properties of ALA and enhancing the transport of ALA into cells. For example, the attempted synthesis of novel ester bioconjugates of ALA with vitamin E (or α-tocopherol) 8 or vitamin D 3 12 has been reported by Vallinayagam et al 34 as shown in Scheme 4. Typically, more complex ester prodrugs of ALA such as the desired conjugates 11 and 15 are prepared using a N-alkoxycarbonyl-protected ALA derivative such as Boc-ALA 9 or the ALA surrogate, azidolevulinic acid 10, with activation of the carboxylic acid function using Steglich-type esterification conditions with a carbodiimide reagent (DCC or EDC) and DMAP as catalyst.…”