Functionalization of chlorin e₆ trimethylester towards potential amphiphilic photosensitizers for photodynamic therapy

Abstract

Chlorins (dihydroporphyrins) are considered, due to their ideal photophysical properties, as attractive photosensitizers for photodynamic therapy (PDT) of cancer and other therapeutic and diagnostic applications. Chlorophyll [Formula: see text], as a naturally occurring chlorin, forms an almost unlimited renewable resource for preparation of potential biologically active chlorin photosensitizers and fluorescence markers. To achieve amphiphilic photosensitizers which might be selectively enriched in tumor cells, we addressed linkage of per se lipophilic chlorophyll derivatives with carbohydrate based hydrophilic aminopolyols.

Transformation Chlorophyll a of Spirulina platensis to Chlorin e6 Derivatives and Several Applications

“…Chlorophyll was extracted and purified from dried S. platensis powder provided by the Hidumi Company, Nghe An province, Viet Nam. Isolation of methyl pheophorbide a2 as a mixture of 13 2 R:13 2 S diastereomers from S. platensis was carried out by the method of Bauer D et al, (2019) [5]. Spirulina powder (700-800 g) was taken into a Sohxlet thimble (length 32.5 cm, diameter 8 cm).…”

“…Methyl pheophobide a was transferred to Ce6 trimethylester by two methods: (1) Methylphephorbide a (2.4 g, 2.8 mmol) was dissolved under an Ar atmosphere in degassed dry THF (25 mL) and CHCl 3 (125 mL) was added followed by 1 M KOH in MeOH (12 mL) and (2) methylpheophorbide a (186.5 mg, 0.25 mmol) was dissolved under an Ar atmosphere in THF (12 mL) and then MeOH (125 mL) was added followed by KOCH 3 in MeOH (2.5 mL 35% solution). Then, they were treated according to method of Bauer D et al, (2019) [5].…”

“…derivatives were obtained by transformation of chlorophyll a using standard protocol described by Bauer D et al, (2019). Briefly, 900 g of dry biomass of S. platensis containing more than 0.4% of chlorophyll was subjected into a 10 mm x 38 mm Soxhlet thimble with 400 mL of acetone in addition of nitrogen liquid.…”

“…The residue was then dried, suspended in 750 mL of dry MeOH and 37. 5 The 2.4 g of the first variant (variant A) of methyl pheophorbide a 2 was dissolved in 25 mL dry THF, 125 mL CHCl 3 and 12 mL 1 M KOH in MeOH was added. The mixture was stirred and poured into 500 mL ice water.…”

“…Chlorophylls are starting materials to synthesize functionalized chlorins that have the ability to improve the photodynamic activity [4]. Chlorophyll a, as a natural chlorin, is a potential renewable resource to product chlorin photosensitizers [5] which can use for photodynamic therapy to treat cancer. Chlorins, that are a class of tetrapyrroles derived from plant, are potential photosensitizers because they can absorb remarkably strongly in the light with high phototoxic red spectrum [6].…”