Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine fused chlorins as very active photodynamic agents for melanoma cells

Pereira, Neide; Laranjo, Mafalda; Piñeiro, Marta; Serra, Arménio C.; Santos, K.; Teixo, Ricardo; Abrantes, Ana Margarida; Gonçalves, Ana Cristina; Sarmento‐Ribeiro, Ana Bela; Casalta-Lopes, João; Botelho, Maria Filomena; Melo, Teresa M. V. D. Pinho e

doi:10.1016/j.ejmech.2015.08.059

Cited by 21 publications

(24 citation statements)

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“…18,19 Furthermore, preliminary studies on the photodynamic activity of 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins against melanoma cells showed that they are very active photodynamic agents. 20 Interestingly, a dihydroxymethylchlorin derivative was particularly active against human melanocytic melanoma A375 cells. This is of particularly importance considering the known resistance of melanoma to conventional chemotherapy and radiotherapy, and the fact that PDT of melanoma can be compromised due to the natural resistance mechanism of some melanotic melanomas.…”

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confidence: 99%

Platinum(II) Ring-Fused Chlorins as Near-Infrared Emitting Oxygen Sensors and Photodynamic Agents

Pereira

Laranjo

Casalta-Lopes

et al. 2017

ACS Med. Chem. Lett.

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Novel near-infrared luminescent compounds based on platinum(II) 4,5,6,7-tetrahydropyrazolo[1,5-a]-pyridine-fused chlorins are described. These compounds have high photostability and display light emission, in particular simultaneous fluorescence and phosphorescence emission in solution at room temperature, in the biologically relevant 700−850 nm red and near-infrared (NIR) spectral region, making them excellent materials for biological imaging. The simultaneous presence of fluorescence and phosphorescence emission at room temperature, with the phosphorescence strongly quenched by oxygen whereas fluorescence remains unaffected, allows these compounds to be used as ratiometric oxygen sensors in chemical and biological media. Both steady-state (fluorescence vs phosphorescence intensities) and dynamic (dependence of phosphorescence lifetimes upon oxygen concentration) luminescence approaches can be used. Photocytotoxicity studies against human melanocytic melanoma cells (A375) indicate that these compounds display potential as photosensitizers in photodynamic therapy.

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confidence: 99%

Platinum(II) Ring-Fused Chlorins as Near-Infrared Emitting Oxygen Sensors and Photodynamic Agents

Pereira

Laranjo

Casalta-Lopes

et al. 2017

ACS Med. Chem. Lett.

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“…PDT is based on the selective retention of photosensitisers in malignant cells and the subsequent destruction of tumours by appropriate wavelength irradiation. 52 PDT largely depends on the properties of the photosensitising agent, [53][54][55] generating photophysical and photochemical reactions, and exerting its outcomes by producing reactive oxygen species (ROS). 56,57 ROS rapidly lead to significant toxicity in the target tissue microenvironment, resulting in tumour cell death by apoptosis, necrosis or autophagy.…”

Section: Laser Therapymentioning

confidence: 99%

Evaluation of eye melanoma treatments in rabbits: A systematic review

et al. 2021

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Melanomas are the most common cancer of the eye in canines, felines and humans. The treatment approaches vary, since no gold standard exists. Therefore, this systematic review aimed to compare the treatment modalities in ocular melanoma in rabbits. Medline/PubMed, Cochrane Library, Web of Science and Embase were searched for articles published until 21 April 2021 in English, Portuguese or Spanish, reporting animal studies evaluating photodynamic therapy (PDT), laser, radiotherapy or surgical excision. Twenty-seven articles were included for the qualitative synthesis, with publication dates from 1970 to 2018. Of the selected studies, 19 used PDT, six used radiotherapy and two used laser as treatment. No studies regarding surgical therapy that met the inclusion criteria were obtained. The tumour therapy results were evaluated in a heterogeneous manner for different periods and various methods, including microscopy, angiographic, histological examination, fundoscopy, ultrasound exam and electroretinogram. The treatment modalities analysed successfully treated the ocular melanoma, with tumour necrosis being commonly observed. Despite the therapeutic efficacy shown, side effects have been reported for all the therapies. The studies showed high heterogeneity, and therefore, in the future, new studies should be carried out to increase knowledge about ocular melanoma treatment. The analysed therapies can be used successfully in the treatment of ocular melanoma, with more conservative options such as PDT presenting great potential.

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“…In fact, it was shown that porphyrins react with in situ generated diazafulvenium methides to deliver a new type of stable 4,5,6,7-tetrahydropyrazolo[1,5- a ]pyridine-fused chlorins with favorable photophysical features regarding PDT. Some derivatives have proven to be highly active PSs in different cancer cell lines ( Pereira et al, 2015 ; Pereira et al, 2018 ; Nascimento et al, 2019 ; Pereira et al, 2021 ). A similar synthetic approach has also been recently followed by us in order to obtain novel platinum (II) complexes of these types of ring-fused chlorins, showing an improved NIR luminescence, ratiometric molecular oxygen sensing, and photodynamic action properties in vitro and in vivo , which make them promising leads for cancer theranostic applications ( Pereira et al, 2017 ; Laranjo et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…We observed that increasing the hydrophilicity of these macrocycles is crucial to ensure nanomolar activity against these cells. For instance, dihydroxymethyl chlorin 5a ( Scheme 1 ) exhibited higher levels of intracellular accumulation and phototoxic activity towards A375 melanoma cells than its corresponding diester-substituted derivative 4a ( Pereira et al, 2015 ). Notwithstanding the proven and formidable photodynamic performance of some of the studied PSs, it was decided to lengthen the scope of our study by exploring chlorins bearing substituents of different chemical nature, namely hydroxymethyl and carboxylic acid moieties at the exocyclic ring.…”

Section: Introductionmentioning

confidence: 99%

Ring-Fused meso-Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation

et al. 2022

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Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused meso-tetraarylchlorins, with different degrees of hydrophilicity (with methyl ester, hydroxymethyl, and carboxylic acid moieties), have been synthesized and their photophysical characterization as well as in vitro photocytotoxicity assessment against human melanoma and esophageal and bladder carcinomas was carried out. An integrated analysis of the photosensitizers’ performance, considering the singlet oxygen generation data, cell internalization, and intracellular localization, allowed to establish relevant structure-photoactivity relationships and the rationalization of the observed photocytotoxicity. In the diacid and monoalcohol series, chlorins derived from meso-tetraphenylporphyrin proved to be the most efficient photodynamic therapy agents, showing IC50 values of 68 and 344 nM against A375 cells, respectively. These compounds were less active against OE19 and HT1376 cells, the diacid chlorin with IC50 values still in the nano-molar range, whereas the monohydroxymethyl-chlorin showed significantly higher IC50 values. The lead di(hydroxymethyl)-substituted meso-tetraphenylchlorin confirmed its remarkable photoactivity with IC50 values below 75 nM against the studied cancer cell lines. Subcellular accumulation of this chlorin in the mitochondria, endoplasmic reticulum, and plasma membrane was demonstrated.

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Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine fused chlorins as very active photodynamic agents for melanoma cells

Cited by 21 publications

References 45 publications

Platinum(II) Ring-Fused Chlorins as Near-Infrared Emitting Oxygen Sensors and Photodynamic Agents

Platinum(II) Ring-Fused Chlorins as Near-Infrared Emitting Oxygen Sensors and Photodynamic Agents

Evaluation of eye melanoma treatments in rabbits: A systematic review

Ring-Fused meso-Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation

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