Syntheses and cellular investigations of di-aspartate and aspartate-lysine chlorin e₆ conjugates

Abstract

Chlorin e6 is a tricarboxylic acid degradation product of chlorophyll a. Four chlorin e6 bis(amino acid) conjugates were regioselectively synthesized bearing two aspartate conjugates in the 131,173- and 152,173-positions, or at the 131,152 via an ethylene diamine linker. One additional conjugate bearing two different amino acids, lysine at 131 via an ethylene diamine linker and an aspartate at 152 via a β-alanine linker was also synthesized. The cytotoxicity and uptake of four di(amino acid) chlorin e6 conjugates were investigated in human HEp2 cells, and compared with chlorin e6. The most cytotoxic and most taken up conjugates were the zwitterionic 131,152-disubstituted conjugates 28 and 33; these also localized in multiple organelles. In contrast, the tetra-anionic 131,173- and 152,173-di-aspartyl chlorin e6 conjugates 12 and 13 showed low dark cytoxicity and lower phototoxicity compared with chlorin e6.

Conjugates of Pyropheophorbide a with Androgen Receptor Ligands

“…Then the residue was dissolved in THF (30 mL), the solution was dried over granulated KOH, followed by evaporation to dryness. The obtained black powder (139 mg, 0.24 mmol, 83 %) was used without further purification; the analytical sample was purified by TLC in (9). Compound 9 was synthesized from pentafluorophenylpyropheophorbide a 7a (88 mg, 0.13 mmol) and mono-Boc-ethylene diamine (42 mg, 0.26 mmol) according the procedure described in ref.…”

“…[1][2][3] Synthesized earlier conjugates of macrocycles with polyamines, amino acids, peptides, peptidomimetics, antibiotics, nucleotides, carbohydrates, bile acids, lipids, steroids, etc., revealed prospective implications in biomedical studies and photodynamic therapy. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] In this study we have synthesized conjugates of pyropheophorbide a with androgen receptor ligandstestosterone and dihydrotestosterone. Аndrogen receptor is known to be an important drug target for treatment of prostate cancer.…”

Syntheses and PDT activity of new mono- and di-conjugated derivatives of chlorin e6

“…The main factor influencing the biological activity of any individual compound appeared to be the amino acid conjugation site, with the 17 3 -conjugates (identified in the patent [6] as being the structure of, for example, NPe 6 ) being the least active sensitizers. These studies were followed up with new syntheses and cellular studies of di-aspartate and aspartate-lysine chlorin e 6 conjugates [13]. Regioselective synthetic procedures to four chlorin e 6 bis(amino acid) conjugates were developed for bis-conjugates bearing two aspartate residues in the 13 1 ,17 3 - and 15 2 ,17 3 -positions, as well as at the 13 1 ,15 2 sites connected via an ethylene diamine insert.…”

“…the 13 1 ,17 3 -and 15 2 ,17 3 -di-aspartyl conjugates) showed low dark cytoxicity but lower phototoxicity properties compared with chlorin e 6 itself. Indeed, all of the bis-conjugates synthesized were inferior as PDT sensitizers compared with the corresponding mono-conjugates [13]. …”

“…In particular, four non-amino acid 15 2 -conjugates ( 7 – 10 ) of chlorin e 6 were synthesized [12], as well as a bis-conjuate with ethylenediamine [13]. In the present paper we report the syntheses of three additional mono-conjugates and of one bis-conjugate (for comparison purposes), and also report the results of cellular studies designed to assess their potential as effective PDT agents.…”