DNA Targeting by Cationic Porphyrin–Ruthenium(II) Conjugates

Musetti, Caterina; Spagnul, Cinzia; Mion, Giuliana; Ros, Sivia Da; Gianferrara, Teresa; Sissi, Claudia

doi:10.1002/cplu.201402275

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…DNA is also one of the most specific biological targets for cationic porphyrins. The formation of strong complexes of these compounds with nucleic acids has been reported, including for the recognition of noncanonical structures of DNA called G-quadruplexes [ 41 ]. Other authors [ 42 ] have shown that the HSV-1 genome contains multiple clusters of repeated G-quadruplex.…”

Section: Introductionmentioning

confidence: 99%

Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity against HSV-1

et al. 2021

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This work is devoted to the search for new antiherpes simplex virus type 1 (HSV-1) drugs among synthetic tetrapyrroles and to an investigation of their antiviral properties under nonphotodynamic conditions. In this study, novel amphiphilic 5,10,15,20-tetrakis(4-(3-pyridyl-n-propanoyl)oxyphenyl)porphyrin tetrabromide (3a), 5,10,15,20-tetrakis(4-(6-pyridyl-n-hexanoyl)oxyphenyl)porphyrin tetrabromide (3b) and known 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetraiodide (TMePyP) were synthesized, and their dark antiviral activity in vitro against HSV-1 was studied. The influence of porphyrin’s nanosized delivery vehicles based on Pluronic F127 on anti-HSV-1 activity was estimated. All the received compounds 3a, 3b and TMePyP showed virucidal efficiency and had an effect on viral replication stages. The new compound 3b showed the highest antiviral activity, close to 100%, with the lowest concentration, while the maximum TMePyP activity was observed with a high concentration; porphyrin 3a was the least active. The inclusion of the synthesized compounds in Pluronic F-127 polymeric micelles had a noticeable effect on antiviral activity only at higher porphyrin concentrations. Action of the received compounds differs by influence on the early or later reproduction stages. While 3a and TMePyP acted on all stages of the viral replication cycle, porphyrin 3b inhibited viral replication during the early stages of infection. The resulting compounds are promising for the development of utilitarian antiviral agents and, possibly, medical antiviral drugs.

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Section: Introductionmentioning

confidence: 99%

Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity against HSV-1

et al. 2021

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“…In solution, these molecules caused strong light-induced photodamage to DNA. In some cases, pronounced dark toxicity was also observed …”

Section: Conjugation Of Photosensitizers With Cytotoxic Drugsmentioning

confidence: 97%

“…In some cases, pronounced dark toxicity was also observed. 100 The mechanism of cytotoxicity exerted by ruthenium moieties independent of a conjugated porphyrinoid has not yet fully established. Unlike platinum derivatives, ruthenium conjugates were not found in nucleus and therefore could not damage DNA.…”

Section: Cytotoxic Drugsmentioning

confidence: 99%

Conjugates of Porphyrinoid-Based Photosensitizers with Cytotoxic Drugs: Current Progress and Future Directions toward Selective Photodynamic Therapy

et al. 2022

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Photodynamic therapy (PDT) is a treatment modality where light-mediated activation of photosensitizers in a patient’s body leads to the generation of cytotoxic reactive oxygen species (ROS), eliminating cancer cells. One direction that has been firmly established over past years is the conjugation of photosensitizers with various molecules that demonstrate their own cytotoxic activity. As a result, improved selectivity and treatment outcomes are observed compared to those of unconjugated drugs. The attractiveness of such an approach is due to the variability of cytotoxic warheads and specific linkers available for the construction of conjugates. In this review, we summarize and analyze data concerning these inventions with the ultimate goal to find a promising conjugation partner for a porphyrinoid-based photosensitizer. The current challenges toward successful conjugation are also outlined and discussed. We hope that this review will motivate researchers to pay closer attention to conjugates and possibilities hidden in these molecules for the PDT of cancer.

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“…The PS forms a long-lived triplet state that can react with molecular oxygen to generate reactive oxygen species (ROS), including singlet oxygen and hydroxyl radicals, leading, in situ, to cell death by necrotic and apoptotic modes [13,14]. As a result, significant advantages of PDT on antimicrobial chemotherapy are observed: it offers a short inactivation time to lead to cell death pathways; it does not lead to bacterial resistance after multi-course treatment; it does not cause dysbacteriosis; and it is applied to a wide range of target microorganisms, including Gram-positive and Gram-negative bacteria [7,9,15]. The widespread use of PDT in the treatment of skin tumors, actinic keratosis, acne, and rosacea is noteworthy and recognized by the Brazilian Society of Dermatological Surgery.…”

Section: Introductionmentioning

confidence: 99%

Photo-Phytotherapeutic Gel Composed of Copaifera reticulata, Chlorophylls, and k-Carrageenan: A New Perspective for Topical Healing

et al. 2022

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Chronic wound healing represents an impactful financial burden on healthcare systems. In this context, the use of natural products as an alternative therapy reduces costs and maintains effectiveness. Phytotherapeutic gels applied in photodynamic therapy (PDT) have been developed to act as topical healing medicines and antibiotics. The bioactive system is composed of Spirulina sp. (source of chlorophylls) and Copaifera reticulata oil microdroplets, both incorporated into a polymeric blend constituted by kappa-carrageenan (k-car) and F127 copolymer, constituting a system in which all components are bioactive agents. The flow behavior and viscoelasticity of the formulations were investigated. The photodynamic activity was accessed from studies of the inactivation of Staphylococcus aureus bacteria, the main pathogen of hospital relevance. Furthermore, in vivo studies were conducted using eighteen rabbits with dermatitis (grade III and IV) in both paws. The gels showed significant antibiotic potential in vitro, eliminating up to 100% of S. aureus colonies in the presence or absence of light. The k-car reduced 41% of the viable cells; however, its benefits were enhanced by adding chlorophyll and copaiba oil. The animals treated with the phytotherapeutic medicine showed a reduction in lesion size, with healing and re-epithelialization verified in the histological analyses. The animals submitted to PDT displayed noticeable improvement, indicating this therapy’s viability for ulcerative and infected wounds. This behavior was not observed in the iodine control treatment, which worsened the animals’ condition. Therefore, gel formulations were a viable alternative for future pharmaceutical applications, aiming at topical healing.

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DNA Targeting by Cationic Porphyrin–Ruthenium(II) Conjugates

Abstract: Scheme 2. Synthesis of P5: [Ru ([9]aneS3)(dmso)Cl 2 ], CH 3 OH/CH 2 Cl 2 6:1, heated at reflux, 24 h (71 %).

Cited by 7 publications

References 37 publications

Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity against HSV-1

Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity against HSV-1

Conjugates of Porphyrinoid-Based Photosensitizers with Cytotoxic Drugs: Current Progress and Future Directions toward Selective Photodynamic Therapy

Photo-Phytotherapeutic Gel Composed of Copaifera reticulata, Chlorophylls, and k-Carrageenan: A New Perspective for Topical Healing

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