Synthesis and Characterization of Novel Purpurinimides as Photosensitizers for Photodynamic Therapy

Cui, Bing Cun; Yoon, Il; Li, Jia Zhu; Lee, Woo Kyoung; Shim, Young Key

doi:10.3390/ijms15058091

Cited by 16 publications

(10 citation statements)

References 14 publications

(14 reference statements)

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“…Up to a concentration of 10 µM, compound 1 did not induce any dark toxicity in the MCF-7, PC-3, MIA PaCa-2 and U-2 OS cells. This corresponds to the assumption that compound 1 (and thereby potentially also its derivatives) has low dark toxicity, as reported for a number of human cancer cell lines (HL-60 [8], Colo-205 [36], Hep-G2 [42], A549 [53,54], MCF-7 [55]). Darmostuk et al [6] determined that the IC 50 (dark toxicity) of compound 1 exceeded 100 µM in HaCaT and VH10 cells and was 54 µM for NIH 3T3 cells.…”

Section: Photo-and Dark Toxicity Of the Compounds In Vitromentioning

confidence: 62%

“…Because logP is related to the cell uptake level of a compound, logP was calculated for our purpurin 18 derivatives. The data presented in Table 5 show that all compounds had logP of less than 5, which indicates that they should yield a good PDT response [54]. The derivatization of compound 1 with a metal ion and/or a PEG spacer led to lower logP values; the corresponding increase in hydrophilicity is an important factor for the use of such a compound in PDT.…”

Section: Logarithm Of Partition Coefficientsmentioning

confidence: 98%

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PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

et al. 2019

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Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC50 (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer.

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Section: Photo-and Dark Toxicity Of the Compounds In Vitromentioning

confidence: 62%

Section: Logarithm Of Partition Coefficientsmentioning

confidence: 98%

PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

et al. 2019

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“…Produtos naturais com importantes atividades biológicas em diferentes sistemas também foram isolados a partir do noni. Dentre eles, um metabólito da clorofila chamado feoforbida (FIGURA 2A) apresenta potencial interesse, como foto sensor na terapia fotodinâmica para tratamento do câncer (Cui et al, 2014). Muitos estudos, sobre esse tema, estão sendo publicados, o que reflete a relevância desta molécula como alternativa terapêutica, desenvolvida com o auxílio da nanotecnologia (Till et al, 2016).…”

Section: Aspectos Químicosunclassified

Morinda citrifolia: fatos e riscos sobre o uso do noni

et al. 2018

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Morinda citrifolia L. (Rubiaceae), popularmente conhecida como noni, é amplamente utilizada na Polinésia e no Havaí, para tratamento de diversas patologias, como: dislipidemia, diabetes, câncer, hipertensão, cicatrização, dentre outras. Atualmente, observa-se também o uso exacerbado no Brasil, especialmente na região Nordeste, onde a planta se adaptou bem. Porém, ainda não há certeza da sua eficácia, e muitas pesquisas sobre a ação terapêutica do noni estão em desenvolvimento, embora os resultados sejam bastante controversos. O que torna o noni uma planta diferenciada e que requer atenção especial é seu potencial hepatotóxico. A Agência Nacional de Vigilância Sanitária (ANVISA) fundamenta a sua recomendação de não utilizar o noni, também, com base em relatos de toxicidade em humanos. Este trabalho é uma revisão da literatura, com objetivo de avaliar o potencial terapêutico desta planta de acordo com os estudos já desenvolvidos. Dessa forma, é possível realizar uma análise crítica do uso irracional desta planta e contribuir com a divulgação de possíveis riscos à saúde.

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“…In addition, chlorins are abundantly available from natural sources such as plants (chlorophyll paste) and algae ( Spirulina maxima ) [ 16 ], and can be synthesized in a straightforward manner into chlorin derivatives with various active functional groups on the chlorin moiety [ 17 ]. Recently, our group synthesized several chlorin derivatives to evaluate structure–activity relationship [ 18 , 19 , 20 , 21 , 22 , 23 ]. Among the chlorin derivatives synthesized by our group, we report the activity of two chlorins as photosensitizers, methyl pyropheophorbide a (MPPa) and N -methoxyl purpurinimide (NMPi), in this present study [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy

Chang

Liu

Lee

et al. 2018

IJMS

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Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of <50 mm3) and large (tumor volume of >50 mm3) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.

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Synthesis and Characterization of Novel Purpurinimides as Photosensitizers for Photodynamic Therapy

Cited by 16 publications

References 14 publications

PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

Morinda citrifolia: fatos e riscos sobre o uso do noni

Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy

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