Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

Abstract

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.

Novel Nile Blue Analogue Stains Yeast Vacuolar Membrane, Endoplasmic Reticulum, and Lipid Droplets, Inducing Cell Death through Vacuole Membrane Permeabilization

“…On the other hand, BaP1 shows immense potential to be explored not only as an antifungal but also in other pharmacological applications. Phenoxazine compounds have grown as molecules of great interest in anticancer therapy [18][19][20][21][22][23]66] as well as antibacterial [67,68] and antiviral agents [69]. In this perspective, BaP1's vacuolar membrane-permeabilizing capacity could emerge as a promising therapeutical approach.…”

Development of New Natural Lipid-Based Nanoparticles Loaded with Aluminum-Phthalocyanine for Photodynamic Therapy against Melanoma

“…It was found that SLN-AlPc containing final AlPc concentrations of 20 μM and 40 μM (SLN-AlPc-20 and SLN-AlPc-40, respectively) presented absorbance peaks of 676 nm and 674 nm, respectively ( Figure S4 ). This is an important characteristic to be considered when evaluating its use in anticancer PDT, since the ideal therapeutic window for PDT is in the spectral region from 600–800 nm, where radiation penetration into living tissue is greater and absorption by endogenous chromophores (water, proteins, and pigments such as melanin and bilirubin) is lower [ 42 , 43 ].…”

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

“…It is worth mentioning that, mainly in dermatology, even UVB irradiation is considered of therapeutic use [16][17][18]. Besides the anticancer activities of photosensitizers [19][20][21], "post-antibiotic era" is experimenting with photosensitizers as alternative therapeutics for the fight against multiresistant bacteria both for medicinal [22][23][24][25] and environmental purposes [26,27].…”

“…Based on our interest in the chemistry and biology of the oxime functionality [54][55][56][57], as well as in their DNA photolytic interaction upon UV irradiation [9][10][11]43] we have decided to investigate the behaviour of carefully designed O-carbamoyl derivatives of p-pyridine amidoxime, ethanone oxime and aldoxime (VI, VII, VIII, R 1 = p-pyridyl, Figure 1) as DNA photosensitizers. Based on our previous ex-Scheme 1: Synthesis of O-carbamoyl amidoximes (8)(9)(10)(11)(12)(13), ethanone oximes (15)(16)(17)(18)(19)(20) and aldoximes (22)(23)(24)(25)(26)(27). Oxime 1 or 14 or 21, Et 3 N (1.1 equiv), R-NCO (1.1-1.8 equiv), dry chloroform or tetrahydrofuran, Ar, 0 °C → rt or reflux, 19-97%.…”