Water-Soluble Glucosyl Pyrene Photosensitizers: An Intramolecularly Synthesized 2-C-Glucoside and an O-Glucoside

Abstract

Prevalent photosensitizing agents for photodynamic therapy (PDT) suffer from their relatively large molecular weights causing photodermatosis. In this regard, low molecular weight pyrene could be an efficient photosensitizer except for its extreme hydrophobicity. To tackle the insolubility of pyrene, we synthesized 1-carboxypyren-2-yl C-glucoside 4 by a tethered C-glucosylation and 1-pyrenylmethyl O-glucoside 5 by a simple O-glucosylation. Compounds 4 and 5 showed modest water solubilities of 72 and 47 μg/mL, respectively. Whereas compound 4 partially underwent a cyclization reaction at pH 3 to give the corresponding δ-valerolactone 15b in 31% yield after 24 h, it is stable at pH 5–9 for at least a week. The 1O2-producing photosensitizabilities of 4 and 5 were sufficient to apply to PDT. Although compound 5 was uptaken by HeLa cells and showed a good PDT activity, compound 4 showed neither a sufficient cell uptake nor PDT effect. The binding modes of compounds 4 and 5 to concanavalin A were specific and unspecific, respectively. These results demonstrate that compounds 4 and 5 are within a pharmacologically acceptable range as oral drugs and could be a fluorescence imaging probe for α-glucose/mannose receptors and a photosensitizing agent for PDT, respectively.

Fluorescent glycoconjugates and their applications

“…Water-soluble 2-C-glucosyl and O-glucosyl pyrenes were studied as photosensitizers for applications in photodynamic therapy ( Figure 74). 195 Water-solubility of 50-75 µg/mL was observed and the compounds could produce singlet oxygen in vitro. While the O-glucoside could be readily detected in HeLa cells and was successfully engaged in PDT, the C-glucoside did not enter HeLa cells.…”

New Hybrid (E)‐4‐((pyren‐1‐ylmethylene)amino)‐N‐(thiazol‐2‐yl)benzenesulfonamide as a Potential Drug Candidate: Spectroscopy, TD‐DFT, NBO, FMO, and MEP Studies**

“…The 1 H and 13 C NMR spectra of the compound were given in Figures 3-4, respectively. The numerical data obtained from both the experiment and GIAO approaches were given in Table 3.…”

“…[12] This core is a chromophore with very common uses such as chemical sensors, probes for micelle and cell membrane properties, OLED, ligands for fluorescent coordination complexes, and photosensitizers that produce singlet oxygen. [13] Pyrene-based molecular systems are an essential role in elucidating the interactions that occurred in the biomolecular systems since their unique fluorescence properties, availability of forming the excimers, and sensitivity to the polarity of the media being in. [14,15] In this regard, the photochemical properties of 2-and 2,7-substituted pyrene derivatives, due to the availability using in detection were enlightened by both the analytical techniques and the computational approaches.…”

Impact of the Histidine-Triazole and Tryptophan-Pyrene Exchange in the WHW Peptide: Cu(II) Binding, DNA/RNA Interactions and Bioactivity

“…Additionally, pyrene-peptide conjugates were recently efficiently applied for the fine sensing of various nucleic acid sequences [35][36][37]. Additionally, pyrenes may serve as anticancer agents and chemotherapeutics [38,39]. A particularly intriguing property of pyrene for this research is the ability to produce singlet oxygen upon irradiation [31], which could eventually lead to photo-induced DNA cleavage or bioactivity [39,40].…”

“…Additionally, pyrenes may serve as anticancer agents and chemotherapeutics [38,39]. A particularly intriguing property of pyrene for this research is the ability to produce singlet oxygen upon irradiation [31], which could eventually lead to photo-induced DNA cleavage or bioactivity [39,40]. Taking into account recent advancements in Two-Photon-Absorption (TPA) techniques applied for photodynamic therapy (PDT) [41,42], pyrenes can now be applied as very efficient photosensitisers [40][41][42][43].…”