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International Journal of Molecular... Aug 2019Recent scientific research has shown the use of chlorin, phthalocyanines, and porphyrins derivatives as photosensitizers in photodynamic therapy in the treatment of... (Review)
Review
Recent scientific research has shown the use of chlorin, phthalocyanines, and porphyrins derivatives as photosensitizers in photodynamic therapy in the treatment of various pathologies, including some of the major skin diseases. Thus, the main goal of this critical review is to catalog the papers that used these photosensitizers in the treatment of acne vulgaris, psoriasis, papillomavirus infections, cutaneous leishmaniasis, and skin rejuvenation, and to explore the photodynamic therapy mechanisms against these conditions alongside their clinical benefits.
Topics: Animals; Humans; Indoles; Isoindoles; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin; Skin Diseases; Treatment Outcome
PubMed: 31398812
DOI: 10.3390/ijms20163861 -
Molecules (Basel, Switzerland) Apr 2023Using a combination of unconstrained and constrained molecular dynamics simulations, we have evaluated the binding affinities between two porphyrin derivatives (TMPyP4...
Using a combination of unconstrained and constrained molecular dynamics simulations, we have evaluated the binding affinities between two porphyrin derivatives (TMPyP4 and TEGPy) and the G-quadruplex (G4) of a DNA fragment modeling the insulin-linked polymorphic region (ILPR). Refining a well-established potential of mean force (PMF) approach to selections of constraints based on root-mean-square fluctuations results in an excellent agreement between the calculated and observed absolute free binding energy of TMPyP4. The binding affinity of IPLR-G4 toward TEGPy is predicted to be higher than that toward TMPyP4 by 2.5 kcal/mol, which can be traced back to stabilization provided by the polyether side chains of TMPyP4 that can nestle into the grooves of the quadruplex and form hydrogen bonds through the ether oxygen atoms. Because our refined methodology can be applied to large ligands with high flexibility, the present research opens an avenue for further ligand design in this important area.
Topics: Insulin; Ligands; Molecular Dynamics Simulation; G-Quadruplexes; Porphyrins
PubMed: 37110681
DOI: 10.3390/molecules28083447 -
Journal of Enzyme Inhibition and... Dec 2020With the development of photodynamic therapy (PDT), remarkable studies have been conducted to generate photosensitisers (PSs), especially porphyrin PSs. A variety of... (Review)
Review
With the development of photodynamic therapy (PDT), remarkable studies have been conducted to generate photosensitisers (PSs), especially porphyrin PSs. A variety of chemical modifications of the porphyrin skeleton have been introduced to improve cellular delivery, stability, and selectivity for cancerous tissues. This review aims to highlight the developments in porphyrin-based structural modifications, with a specific emphasis on the role of PDT in anticancer treatment and the design of PSs to achieve a synergistic effect on multiple targets.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Drug Design; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 32329382
DOI: 10.1080/14756366.2020.1755669 -
International Journal of Molecular... Aug 2020Porphyrins have planar and conjugated structures, good optical properties, and other special functional properties. Owing to these excellent properties, in recent years,... (Review)
Review
Porphyrins have planar and conjugated structures, good optical properties, and other special functional properties. Owing to these excellent properties, in recent years, porphyrins and their analogues have emerged as a multifunctional platform for chemical sensors. The rich chemistry of these molecules offers many possibilities for metal ions detection. This review mainly discusses two types of molecular porphyrin and porphyrin composite sensors for metal ions detection, because porphyrins can be functionalized to improve their functional properties, which can introduce more chemical and functional sites. According to the different application materials, the section of porphyrin composite sensors is divided into five sub-categories: (1) porphyrin film, (2) porphyrin metal complex, (3) metal-organic frameworks, (4) graphene materials, and (5) other materials, respectively.
Topics: Fluorescent Dyes; Ions; Metal-Organic Frameworks; Metals; Molecular Probes; Porphyrins
PubMed: 32823943
DOI: 10.3390/ijms21165839 -
Basic & Clinical Pharmacology &... Mar 2023Pregnane X receptor (PXR) is known to stimulate haem synthesis, but detailed knowledge on the effects of PXR activation on porphyrin metabolism in humans is lacking. We... (Randomized Controlled Trial)
Randomized Controlled Trial
Pregnane X receptor (PXR) is known to stimulate haem synthesis, but detailed knowledge on the effects of PXR activation on porphyrin metabolism in humans is lacking. We utilized a randomized, crossover, open (blinded laboratory) and placebo-controlled trial with 600-mg rifampicin or placebo dosed for a week to investigate the effects of PXR activation on erythrocyte, plasma, faecal and urine porphyrins. Sixteen healthy volunteers participated on the trial, but the number of volunteers for blood and urine porphyrin analyses was 15 while the number of samples for faecal analyses was 14. Rifampicin increased urine pentaporphyrin concentration 3.7-fold (mean 1.80 ± 0.6 vs. 6.73 ± 4.4 nmol/L, p = 0.003) in comparison with placebo. Urine coproporphyrin I increased 23% (p = 0.036). Faecal protoporphyrin IX decreased (mean 31.6 ± 23.5 vs. 19.2 ± 27.8 nmol/g, p = 0.023). The number of blood erythrocytes was slightly elevated, and plasma bilirubin, catabolic metabolite of haem, was decreased. In conclusion, rifampicin dosing elevated the excretion of certain urinary porphyrin metabolites and decreased faecal protoporphyrin IX excretion. As urine pentaporphyrin and coproporphyrin I are not precursors in haem biosynthesis, increased excretion may serve as a hepatoprotective shunt when haem synthesis or porphyrin levels are increased.
Topics: Humans; Erythrocytes; Healthy Volunteers; Heme; Porphyrins; Rifampin; Pregnane X Receptor
PubMed: 36535687
DOI: 10.1111/bcpt.13826 -
Theranostics 2023The current clinical treatment of osteomyelitis is limited by the emergence of drug-resistant bacteria, which often leads to the failure of traditional antibiotic...
The current clinical treatment of osteomyelitis is limited by the emergence of drug-resistant bacteria, which often leads to the failure of traditional antibiotic treatment and large bone defects. Sonodynamic therapy (SDT) is a new strategy that is widely used to overcome the problem of bacterial resistance to antibiotic therapy as well as poor tissue penetration using near-infrared light in photodynamic therapy (PDT). Therefore, it is necessary to develop a new sonosensitizer that can kill bacteria and promote bone repair. Herein, we developed a sonosensitizer, porphyrin metal-organic framework (HNTM), with a Schottky junction modified by TiC nanosheets (HN-TiC) for highly efficient sonodynamic therapy of osteomyelitis and bone regeneration. TiC greatly improves the acoustic catalytic performance by rapidly transferring the charge carriers generated by HNTM under ultrasound (US) irradiation, which killing drug-resistant bacteria through the generation of large amounts of reactive oxygen species (ROS). And HN-TiC shows excellent 99.75% antibacterial effectiveness against MRSA. In addition, HN-TiC generates a sonocurrent under low-intensity US to promote the repair of bone defects for a long time period. Mechanistic research using CCK-8 and RNA-seq showed that HN-TiC nanocomposites can promote the proliferation of stem cells by regulating the cell cycle, DNA replication, and apoptosis. In addition, after low-intensity US irradiation, HN-TiC promotes osteogenic differentiation via some key signaling pathways, including the calcium, Wnt, and TGF-beta signaling pathways, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). In a MRSA-infected rat tibial osteomyelitis model, HN-TiC successfully eliminated the infection and significantly improved bone regeneration under US irradiation. This study indicates that engineered HN-TiC is a distinctive nanocomposite for successful osteomyelitis treatment.
Topics: Osteogenesis; Ultrasonography; Porphyrins; Anti-Bacterial Agents
PubMed: 37056559
DOI: 10.7150/thno.81511 -
Molecules (Basel, Switzerland) Mar 2021Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis.... (Review)
Review
Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered. It is therefore not surprising that optical methods are typically the prevalent analytical tool applied in characterization and processes involving porphyrinic compounds. However, a wealth of complementary information can be obtained from NMR spectroscopic techniques. Based on the advantage of providing structural and dynamic information with atomic resolution simultaneously, NMR spectroscopy is a powerful method for studying molecular interactions between porphyrinic compounds and macromolecules. Such interactions are of special interest in medical applications of porphyrinic photosensitizers that are mostly combined with macromolecular carrier systems. The macromolecular surrounding typically stabilizes the encapsulated drug and may also modify its physical properties. Moreover, the interaction with macromolecular physiological components needs to be explored to understand and control mechanisms of action and therapeutic efficacy. This review focuses on such non-covalent interactions of porphyrinic drugs with synthetic polymers as well as with biomolecules such as phospholipids or proteins. A brief introduction into various NMR spectroscopic techniques is given including chemical shift perturbation methods, NOE enhancement spectroscopy, relaxation time measurements and diffusion-ordered spectroscopy. How these NMR tools are used to address porphyrin-macromolecule interactions with respect to their function in biomedical applications is the central point of the current review.
Topics: Humans; Magnetic Resonance Spectroscopy; Micelles; Nucleic Acids; Phospholipids; Photosensitizing Agents; Polymers; Porphyrins; Proteins
PubMed: 33808335
DOI: 10.3390/molecules26071942 -
Applied Microbiology and Biotechnology Dec 2024Heme is an iron-containing porphyrin compound widely used in the fields of healthcare, food, and medicine. Compared to animal blood extraction, it is more advantageous... (Review)
Review
Heme is an iron-containing porphyrin compound widely used in the fields of healthcare, food, and medicine. Compared to animal blood extraction, it is more advantageous to develop a microbial cell factory to produce heme. However, heme biosynthesis in microorganisms is tightly regulated, and its accumulation is highly cytotoxic. The current review describes the biosynthetic pathway of free heme, its fermentation production using different engineered bacteria constructed by metabolic engineering, and strategies for further improving heme synthesis. Heme synthetic pathway in Bacillus subtilis was modified utilizing genome-editing technology, resulting in significantly improved heme synthesis and secretion abilities. This technique avoided the use of multiple antibiotics and enhanced the genetic stability of strain. Hence, engineered B. subtilis could be an attractive cell factory for heme production. Further studies should be performed to enhance the expression of heme synthetic module and optimize the expression of heme exporter and fermentation processes, such as iron supply. KEY POINTS: • Strengthening the heme biosynthetic pathway can significantly increase heme production. • Heme exporter overexpression helps to promote heme secretion, thereby further promoting excessive heme synthesis. • Engineered B. subtilis is an attractive alternative for heme production.
Topics: Animals; Heme; Fermentation; Porphyrins; Anti-Bacterial Agents; Iron
PubMed: 38194135
DOI: 10.1007/s00253-023-12968-5 -
Molecules (Basel, Switzerland) Nov 2019The interest in assembling porphyrin derivatives is widespread and is accounted by the impressive impact of these suprastructures of controlled size and shapes in many... (Review)
Review
The interest in assembling porphyrin derivatives is widespread and is accounted by the impressive impact of these suprastructures of controlled size and shapes in many applications from nanomedicine and sensors to photocatalysis and optoelectronics. The massive use of porphyrin dyes as molecular building blocks of functional materials at different length scales relies on the interdependent pair properties, consisting of their chemical stability/synthetic versatility and their quite unique physicochemical properties. Remarkably, the driven spatial arrangement of these platforms in well-defined suprastructures can synergically amplify the already excellent properties of the individual monomers, improving conjugation and enlarging the intensity of the absorption range of visible light, or forming an internal electric field exploitable in light-harvesting and charge-and energy-transport processes. The countless potentialities offered by these systems means that self-assembly concepts and tools are constantly explored, as confirmed by the significant number of published articles related to porphyrin assemblies in the 2015-2019 period, which is the focus of this review.
Topics: Drug Delivery Systems; Light; Nanomedicine; Nanostructures; Porphyrins
PubMed: 31779097
DOI: 10.3390/molecules24234307 -
Metallomics : Integrated Biometal... Dec 2020Drug-resistant infections pose a significant risk to global health as pathogenic bacteria become increasingly difficult to treat. The rapid selection of resistant... (Review)
Review
Drug-resistant infections pose a significant risk to global health as pathogenic bacteria become increasingly difficult to treat. The rapid selection of resistant strains through poor antibiotic stewardship has reduced the number of viable treatments and increased morbidity of infections, especially among the immunocompromised. To circumvent such challenges, new strategies are required to stay ahead of emerging resistance trends, yet research and funding for antibiotic development lags other classes of therapeutics. Though the use of metals in therapeutics has been around for centuries, recent strategies have devoted a great deal of effort into the pathways through which bacteria acquire and utilize iron, which is critical for the establishment of infection. To target iron uptake systems, siderophore-drug conjugates have been developed that hijack siderophore-based iron uptake for delivery of antibiotics. While this strategy has produced several potential leads, the use of siderophores in infection is diminished over time when bacteria adapt to utilize heme as an iron source, leading to a need for the development of porphyrin mimetics as therapeutics. The use of such strategies as well as the inclusion of gallium, a redox-inert iron mimic, are herein reviewed.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Discovery; Gallium; Humans; Iron; Porphyrins; Siderophores
PubMed: 33242314
DOI: 10.1039/d0mt00206b