Synthesis and in vitro antiprotozoal evaluation of substituted phenalenone analogues

Rosquete, Laura I.; Cabrera-Serra, M. Gabriela; Piñero, José E.; Martín-Rodríguez, Patricia; Fernández-Pérez, Leandro; Luis, Javier G.; McNaughton‐Smith, Grant; Abad-Grillo, Teresa

doi:10.1016/j.bmc.2010.04.062

Cited by 27 publications

(26 citation statements)

References 12 publications

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“…In the last years, numerous and new classes of natural products based on the PN skeleton has been isolated from plants and fungi or has been chemically synthesized. These molecules are of special interest owing to their significant roles as phytoalexins and phytoanticipins in the protection of plants against potentially harmful microorganisms such as fungus and protozoans . In addition, these compounds display ROS‐mediated activity against disease vector mosquito larvae and plant‐parasitic nematodes, which is strongly enhanced in the presence of light .…”

Section: Introductionmentioning

confidence: 99%

Phenalenone‐photodynamic therapy induces apoptosis on human tumor cells mediated by caspase‐8 and p38‐MAPK activation

Salmerón

Quintana

Rosa

et al. 2018

Molecular Carcinogenesis

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Photodynamic therapy (PDT) is a rising and hopeful treatment for solid tumors and others malignancies. PDT uses harmless visible light to activate a tumor-associated photosensitizer (PS). The excited PS generates cytotoxic reactive oxygen species (ROS) that induce damage and death of tumor cells. It is known that certain phytoalexins and phytoanticipins derived from plants often display a PS-like activity due to a phenalenone (PN) moiety-an efficient singlet oxygen photosensitizer-in its skeleton. The aim of this study is to explore the phototoxic properties of PN on the human cell line tumor-derived HL60 (acute promyelocytic leukemia) and to identify the cell-specific targets of ROS involved in the tumor cell death. Our results reveal that PN acts as an excellent PS, showing a potent antitumor cell activity in presence of light. PN-PDT generates intracellular ROS, via oxidation reaction mechanisms type I and II, resulting in an induction of apoptosis. Moreover, both extrinsic (through direct activation of caspase-3) and intrinsic (through mitochondrial depolarization) pathways of apoptosis are induced by PN-PDT. Using pharmacologic inhibitors, we also find that PN-PDT activates caspase-8/tBid and p38-MAPK, triggering the activation of the apoptotic pathways. Although, survival pathways are also promoted through PI3 K/Akt and JNK activation, the net result of PN-PDT is the tumor cell death. The present work identifies to PN, for the first time, as a potent photosensitizer in human tumor cell lines and proposes a mechanism by which ROS induces apoptosis of tumor cell.

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Section: Introductionmentioning

confidence: 99%

Phenalenone‐photodynamic therapy induces apoptosis on human tumor cells mediated by caspase‐8 and p38‐MAPK activation

Salmerón

Quintana

Rosa

et al. 2018

Molecular Carcinogenesis

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“…The involvement in the plant’s defense against phytopathogenic fungi [ 4 , 5 ] and nematodes [ 6 ] would appear to be the major ecological function of phenylphenalenones. Pharmacological [ 7 ], antimicrobial [ 1 , 8 ] and radical scavenging activities [ 9 ] have been also reported. Therefore, new phenylphenalenones and related compounds from natural [ 1 , 8 , 10 ] or synthetic sources [ 11 , 12 ] are desirable.…”

Section: Introductionmentioning

confidence: 99%

Application of the Crystalline Sponge Method to Revise the Structure of the Phenalenone Fuliginone

et al. 2017

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The structure of fuliginone was revised from a phenyl substituted phenalenone to a hydroxyl substituted phenalenone as a result of its re-purification via HPLC with subsequent NMR analysis together with an independent synthesis and analysis of the crystal structure, which was secured via the crystalline sponge method. On-flow High Performance Liquid Chromatography coupled to Nuclear Magnetic Resonance spectroscopy (HPLC-NMR) was employed to confirm the presence of the natural product in the plant extract and to monitor for any possible degradation or conversion of the compound.

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“…reported some 9-heterocyclic substituted phenalenone analogues with good antiplasmodial and antiprotozoal activity against Leishmania amazonensis, Trypanosoma cruzi and Plasmodium falciparum . The above studies indicate the importance of the substituents at 9-position 17 . Therefore, we firstly prepared the 9-substituted PNs analogues (PPNs) to study its photosensitized ability.…”

Section: Resultsmentioning

confidence: 68%

“…PNs are often found in plants infected or attacked by microorganisms and fungi for killing the invaders. These natural PNs or their modified structures exhibited antifungal 10 15 , antiplasmodial 16 and antiprotozoal activity 17 and radical scavenging capacity 18 . PN derivatives have also been developed as dental drugs for photodynamic inactivation of oral key bacteria 19 .…”

mentioning

confidence: 99%

Phytoalexin Phenalenone Derivatives Inactivate Mosquito Larvae and Root-knot Nematode as Type-II Photosensitizer

Song

Feng

Wang

et al. 2017

Sci Rep

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Phytoalexins phenalenones (PNs) are phytochemicals biosynthesized inside the plant in responsive to exterior threat. PNs are excellent type-II photosensitizers, which efficiently produce singlet oxygen upon light irradiation. Based on the core functional structure of PNs, novel PN derivatives were synthesized here and their singlet oxygen generating abilities and their phototoxicity were evaluated. At the presence of light, these PNs have photoinduced toxicity towards Aedes albopictus larvae and nematode Meloidogyne incognita, while the activity lost in the dark. The obvious tissue damage was observed on the treated mosquito larvae and nematode due to the generation of singlet oxygen. Our results revealed the potential of phenalenones as photoactivated agents for mosquito and root-knot nematode management together with light.

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Synthesis and in vitro antiprotozoal evaluation of substituted phenalenone analogues

Cited by 27 publications

References 12 publications

Phenalenone‐photodynamic therapy induces apoptosis on human tumor cells mediated by caspase‐8 and p38‐MAPK activation

Phenalenone‐photodynamic therapy induces apoptosis on human tumor cells mediated by caspase‐8 and p38‐MAPK activation

Application of the Crystalline Sponge Method to Revise the Structure of the Phenalenone Fuliginone

Phytoalexin Phenalenone Derivatives Inactivate Mosquito Larvae and Root-knot Nematode as Type-II Photosensitizer

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