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Journal of Photochemistry and... Sep 2021Photodynamic therapy (PDT) is an approved therapeutic approach and an alternative to conventional chemotherapy for the treatment of several types of cancer with the...
Photodynamic therapy (PDT) is an approved therapeutic approach and an alternative to conventional chemotherapy for the treatment of several types of cancer with the advantages of reducing the side effects and developing resistance mechanisms. Here, was evaluated the photosensitization capabilities of 5,10,15,20-tetrakis[4-(pyridinium-1-yl-methyl)phenyl]porphyrin (3), its N-confused isomer (4) and of the neutral precursors (1) and (2) and the results were compared with the ones obtained with the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP). Both regular porphyrin derivatives 1 and 3 showed higher efficiency to generate singlet oxygen than TMPyP. The PDT assays towards MCF-7 cells under red light irradiation (λ > 640 nm, 23.7 mW cm) demonstrated that the cationic porphyrin 3 is an efficient photosensitizer to kill MCF-7 breast cancer cells. The study of the cell death mechanisms induced by the photodynamic process showed that the studied porphyrin 3 and TMPyP caused cell death by autophagic flux and necrosis.
Topics: Apoptosis; Breast Neoplasms; Cell Survival; Female; Humans; Light; MCF-7 Cells; Microscopy, Confocal; Photosensitizing Agents; Porphyrins; Singlet Oxygen
PubMed: 34399205
DOI: 10.1016/j.jphotobiol.2021.112258 -
Topics in Current Chemistry (Cham) May 2021The four pyrrole rings and four meso carbons of tetrapyrrolic porphyrins can be arranged in different ways and the resulting porphyrin isomers exhibit very distinct... (Review)
Review
The four pyrrole rings and four meso carbons of tetrapyrrolic porphyrins can be arranged in different ways and the resulting porphyrin isomers exhibit very distinct electronic properties. The extensive research carried out on the porphyrins over the years has revealed that porphyrin can have several possible isomers and some of these have been identified and synthesized. Among the porphyrin isomers synthesized so far, porphycene and N-confused porphyrins have been investigated extensively whereas the other porphyrin isomers such as hemiporphycene, corrphycene and isoporphycene remain underdeveloped because of synthetic difficulties and their inherently unstable nature. Neoporphyrinoids are new members of the porphyrinoid family that were discovered serendipitously in 2011. Neoporphyrinoids are structural analogues of porphyrinoids with a confused pyrrole nitrogen linked to a meso carbon or the adjacent pyrrole carbon. Thus, neoporphyrinoids have an unusual structure in which pyrrole N is a part of a porphyrinoid framework and the lone pair of electrons on nitrogen participate in macrocyclic conjugation. It's been a decade since the discovery and different types of neoporphyrinoids, including regular, contracted and expanded neoporphyrinoids, have been synthesized by rational synthetic methodologies and their spectral, structural, aromatic and coordination properties have been studied. There is huge scope to develop different synthetic routes to produce new types of stable neoporphyrinoids to study their properties and potential applications. This article presents a brief overview of the synthesis, structure and properties of the neoporphyrinoids reported in this decade.
Topics: Models, Molecular; Molecular Structure; Porphyrins
PubMed: 34009495
DOI: 10.1007/s41061-021-00338-6 -
Life Science Alliance Jul 2024All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways,...
All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways, to accumulate heme intermediates, that is, porphyrins. We coined this essential metabolic rewiring "porphyrin overdrive" and determined that it is cancer-essential and cancer-specific. Among the major drivers are genes encoding mid-step enzymes governing the production of heme intermediates. CRISPR/Cas9 editing to engineer leukemia cell lines with impaired heme biosynthetic steps confirmed our whole-genome data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation. Although porphyrin overdrive is absent in differentiated cells or somatic stem cells, it is present in patient-derived tumor progenitor cells, demonstrated by single-cell RNAseq, and in early embryogenesis. In conclusion, we identified a dependence of cancer cells on non-homeostatic heme metabolism, and we targeted this cancer metabolic vulnerability with a novel "bait-and-kill" strategy to eradicate malignant cells.
Topics: Humans; Heme; Porphyrins; Cell Line, Tumor; CRISPR-Cas Systems; Neoplasms; Metabolic Networks and Pathways; Cell Differentiation; Gene Editing; Animals; Mice
PubMed: 38649187
DOI: 10.26508/lsa.202302547 -
Journal of Hazardous Materials Oct 2022A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and...
A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and characterized. As-prepared N,O-rich TpTph COF shows a high adsorption capacity for Cd due to the abundant coordination sites. More interesting, it is found that the formation of COF enlarges the porphyrin ring center space, thus facilitating the Cdcoordination, and the resulting optical signal changes make the ratiometric detection of Cd possible. Furthermore, using carbon fiber (CF) filaments, which are obtained from low cost and easy-to-obtain actived carbon mask, as support, porphyrin COF-based CF@TpTph membrane is prepared through in-situ growth of COF on the support followed by simple mechanical pressing. The CF@TpTph membrane is demonstrated to work well for both Cd removal and enrichment from soil and water samples, and shows the advantages of ease of handling, robust stability, reduced secondary pollution risk to samples, and good reusability. This work provides a powerful tool for Cd removal and enrichment, exhibits that preparing porphyrin-based COFs is a feasible way to promote the interactions between porphyrin ring and Cd, and demonstrates that mechanical pressing is a promising strategy for the design of COF-based monolithic materials to promote the practical applications of COFs.
Topics: Adsorption; Cadmium; Carbon Fiber; Metal-Organic Frameworks; Porphyrins
PubMed: 35853339
DOI: 10.1016/j.jhazmat.2022.129574 -
Chemical Society Reviews Nov 2022Half a century after the synthesis of the first subporphyrinoid, the study of tripyrrole and trisoindole porphyrin analogues constitutes a fervent and rapidly expanding... (Review)
Review
Half a century after the synthesis of the first subporphyrinoid, the study of tripyrrole and trisoindole porphyrin analogues constitutes a fervent and rapidly expanding research area. The outstanding structural, electronic and optical features of these cone-shaped aromatic macrocycles render them attractive candidates for a wide variety of applications, ranging from optoelectronics to biomedicine. To tune their properties and exploit their functionalities, the development of novel methodologies for the synthesis and post-functionalization of these contracted porphyrinoids, as well as a deep understanding of their supramolecular organization and their implementation into multicomponent systems of increasing complexity are of paramount importance. Herein, a review of the most recent advances in the fundamentals and applications of subporphyrinoids is presented, which comprehensively cover the last decade of discoveries. The final aim is to highlight the chemical versatility and intriguing physicochemical features of subporphyrinoids, while providing an updated overview of their most promising applications.
Topics: Porphyrins
PubMed: 36354343
DOI: 10.1039/d2cs00280a -
Organic & Biomolecular Chemistry Feb 2024The development of photodynamic therapy requires access to smart photosensitizers which combine appropriate photophysical and biological properties. Interestingly,...
The development of photodynamic therapy requires access to smart photosensitizers which combine appropriate photophysical and biological properties. Interestingly, supramolecular and dynamic covalent chemistries have recently shown their ability to produce novel architectures and responsive systems through simple self-assembly approaches. Herein, we report the straightforward formation of porphyrin-peptide conjugates and cage compounds which feature on their surface chemical groups promoting cell uptake and specific organelle targeting. We show that they self-assemble, in aqueous media, into positively-charged nanoparticles which generate singlet oxygen upon green light irradiation, while also undergoing a chemically-controlled disassembly due to the presence of reversible covalent linkages. Finally, the biological evaluation in cells revealed that they act as effective photosensitizers and promote synergistic effects in combination with Doxorubicin.
Topics: Porphyrins; Photosensitizing Agents; Photochemotherapy; Singlet Oxygen; Nanoparticles; Peptides
PubMed: 38289387
DOI: 10.1039/d3ob01887c -
Mini Reviews in Medicinal Chemistry 2021As a group of heterocyclic macrocycle organic natural compounds occurring universally in animal tissues and plants, porphyrins are composed of four modified pyrrole... (Review)
Review
As a group of heterocyclic macrocycle organic natural compounds occurring universally in animal tissues and plants, porphyrins are composed of four modified pyrrole subunits. Porphyrin analogues/ derivatives possess multiple biochemical properties because of their unique structures and have been extensively investigated in cancer treatment. Studies have shown that porphyrins and their derivatives have the ability to locate tumor cells in a variety of human cancers, and these compounds not only exhibit potent therapeutic effects as photodynamic agents but also show promising properties in medicinal imaging, such as MRI, photoacoustic imaging, fluorescence imaging, and PET/SPECT imaging. This paper reviews the recent reports of porphyrin derivatives as therapeutic agents used in tumor therapies, such as sonodynamic therapy, photodynamic therapy and radiotherapy, as well as the imaging agents for multimodality tumor imaging. The limitations of porphyrin-based compounds in tumor treatments and future prospects are also summarized.
Topics: Contrast Media; Humans; Magnetic Resonance Imaging; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 33302834
DOI: 10.2174/1389557520999201209212745 -
Current Medicinal Chemistry 2016Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost... (Review)
Review
BACKGROUND
Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers. However, YAP was also found to be closely connected to autophagy, mitochondria and reactive oxygen/nitrogen species. We herein, review the recent studies where VP was used without photoactivation as a YAP/TEAD inhibitor or protein oligomerization promoter, focusing on its effects on the YAP/TEAD gene targets and other biomarkers related to autophagy.
RESULTS
Since the identification of VP as YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the new potential of this molecule in different cancers, where YAP is overexpressed. However, detailed structural information about its interaction with YAP is still lacking. Concomitantly, VP was identified as autophagosome inhibitor by promoting oligomerization of p62. Moreover, VP proves to be tumor-selective proteotoxic (by oligomerization of p62, STAT3) in colorectal cancer. Knowledge on the biological properties of the only YAP inhibitor available to date is vital for its pharmacological use on cellular and animal models.
CONCLUSION
VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.
Topics: Animals; Humans; Macular Degeneration; Photosensitizing Agents; Porphyrins; Verteporfin
PubMed: 26980565
DOI: 10.2174/0929867323666160316125048 -
Journal of Inorganic Biochemistry Jun 2021The advance of porphyrins as artificial nucleases along the years have developed a class of compounds having potential therapeutic applications. Being an extrovert of... (Review)
Review
The advance of porphyrins as artificial nucleases along the years have developed a class of compounds having potential therapeutic applications. Being an extrovert of chemistry, a variety of chemical modifications have been done on porphyrin macrocycle in order to improve the spectroscopic properties and to adapt as artificial receptors that can recognize molecules. The last twenty years has witnessed broad research in the arena of porphyrin- DNA interactions and their evolution from simple to more complex entities. In this review, we summarize the recent advances in the porphyrin-based structural modifications, with a specific emphasis on various effects of porphyrin on DNA cleavage potency. We particularly detailed the nuclease activity of cationic and anionic porphyrins, porphyrin dimers and conjugates as well as heme proteins till the third generation porphyrins as artificial nucleases.
Topics: Anions; Cations; DNA; Endonucleases; Hemeproteins; Humans; Metalloporphyrins; Metals; Molecular Structure; Porphyrins
PubMed: 33819802
DOI: 10.1016/j.jinorgbio.2021.111434 -
Molecules (Basel, Switzerland) Apr 2020Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several... (Review)
Review
Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several diseases. Among them can be highlighted the possibility of application in photodynamic therapy and antimicrobial/antiparasitic PDT, for example, of malaria parasite. However, the low efficiency generally associated with their low solubility in water and bioavailability have precluded biomedical applications. Nanotechnology can provide efficient strategies to enhance bioavailability and incorporate targeted delivery properties to conventional pharmaceuticals, enhancing the effectiveness and reducing the toxicity, thus improving the adhesion to the treatment. In this way, those limitations can be overcome by using two main strategies: (1) Incorporation of hydrophilic substituents into the macrocycle ring while controlling the interaction with biological systems and (2) by including them in nanocarriers and delivery nanosystems. This review will focus on antiparasitic drugs based on porphyrin derivatives developed according to these two strategies, considering their vast and increasing applications befitting the multiple roles of these compounds in nature.
Topics: Antiparasitic Agents; Biosensing Techniques; Drug Compounding; Humans; Indoles; Isoindoles; Molecular Structure; Porphyrins; Structure-Activity Relationship
PubMed: 32365664
DOI: 10.3390/molecules25092080