ABSTRACT
The singlet and triplet excited states of 9-phenylphenalenones undergo ß-phenyl quenching (BPQ) via addition of the carbonyl oxygen to the ortho position of the phenyl substituent. This reaction leads to the formation of naphthoxanthenes , which, in the absence of quenchers, undergo a very rapid electrocyclic ring opening reaction reverting to within a few microseconds. Naphthoxanthene contains a remarkably weak C-H bond, which enables efficient hydrogen transfer reactions to suitable acceptors, giving rise to the production of the naphthoxanthenyl radical or the naphthoxanthenium cation, depending on the solvent polarity. The study uncovers a number of new aspects of BPQ and suggests an excited state-mediated metabolic pathway in the biosynthesis of plant fluorones.
Subject(s)
Phenalenes/chemistry , Carbon/chemistry , Cyclization , Hydrogen/chemistry , Ketones/chemistry , Light , Magnetic Resonance Spectroscopy , Molecular Conformation , Oxygen/metabolism , Quantum Theory , Spectrophotometry, UltravioletABSTRACT
A set of derivatives encompassing structural modifications on the privileged phenalenone scaffold were assessed for their antiparasitic activities against the most clinically relevant forms of trypanosomiasis and leishmaniasis. Several compounds exhibited leishmanicidal effects at levels comparable or better than the reference drug pentamidine, while the parent phenalenone was shown to have a level of activity against Trypanosoma cruzi comparable to the marketed drug benznidazole.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Phenalenes/chemistry , Antiprotozoal Agents/therapeutic use , Antiprotozoal Agents/toxicity , Cell Line, Tumor , Humans , Leishmaniasis/drug therapy , Pentamidine/therapeutic use , Phenalenes/therapeutic use , Phenalenes/toxicity , Trypanosoma cruzi/drug effects , Trypanosomiasis/drug therapyABSTRACT
The new aromatic diterpenes 7beta-O-benzylrosmanol (3), 7beta-O-benzyl-11,12-di-O-methylrosmanol (4), and 7alpha-thiophenylcarnosic acid (5) have been obtained by partial synthesis from carnosol (1), an abundant natural diterpene present in Salvia species. The structures of these compounds were established from their physical and spectroscopic data. The known diterpenes sagequinone methide A (6), 7beta-O-methylrosmanol (7), 7-O-methylrosmanol (8), and rosmaquinone B (9) were obtained from rosmanol (2). The spectroscopic data of these semisynthetic diterpenes were identical to data reported in the literature. In addition, the new semisynthetic isorosmaquinone (10) was obtained from isorosmanol (12). The proton resonances of rosmaquinone (11) are reassigned based on 2D NMR spectroscopy. These compounds, as well as eight known analogues, were evaluated for cytotoxic and antimicrobial activities.
Subject(s)
Abietanes , Antineoplastic Agents, Phytogenic , Diterpenes/chemistry , Plants, Medicinal/chemistry , Quinones/chemistry , Salvia/chemistry , Abietanes/chemistry , Abietanes/isolation & purification , Abietanes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Chlorocebus aethiops , Drug Screening Assays, Antitumor , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , HeLa Cells , Humans , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Structure-Activity Relationship , Vero CellsABSTRACT
A phytochemical study has been carried out on the aerial parts of Salvia pachyphylla and S. clevelandii. From S. pachyphylla, the known diterpenes carnosol (2), rosmanol, 20-deoxocarnosol (3), carnosic acid, isorosmanol (4), 7-methoxyrosmanol, 5,6-didehydro-O-methylsugiol (5), 8beta-hydroxy-9(11),13-abietadien-12-one (6), 11,12-dioxoabieta-8,13-diene, and 11,12-dihydroxy-20-norabieta-5(10),8,11,13-tetraen-1-one were isolated, together with the new diterpene pachyphyllone (1). From S. clevelandii, the known diterpenes rosmadial (7), 16-hydroxycarnosol (8), abieta-8,11,13-triene, and taxodone were obtained, together with carnosol (2), rosmanol, and carnosic acid. The structure of the new compound (1) was identified on the basis of spectroscopic data analysis. Several of these compounds (1-8) were evaluated against a small panel of human cancer cell lines.
Subject(s)
Abietanes/isolation & purification , Abietanes/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Plants, Medicinal/chemistry , Salvia/chemistry , Abietanes/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Mexico , Molecular StructureABSTRACT
Experiments were performed to elucidate the excited-state behavior of 9-phenylphenalenones, which are phototoxic plant secondary metabolites involved in mechanisms of light-mediated plant defense. Using a combination of time-resolved and steady-state UV/visible spectroscopies, time-resolved IR absorption spectroscopy, time-resolved singlet oxygen phosphorescence measurements and cyclic voltammetry, we provide evidence of an intramolecular charge-transfer process in the excited singlet and the triplet states of 9-phenylphenalenones that modulates the photosensitized production of singlet oxygen.
Subject(s)
Phenalenes/chemistry , Plant Extracts/chemistry , Photochemistry , Sesquiterpenes , Singlet Oxygen , Solvents , Spectrophotometry , Spectrophotometry, Ultraviolet , Terpenes , PhytoalexinsABSTRACT
The light-induced singlet oxygen production and antifungal activity of phenylphenalenone phytoalexins isolated from infected banana plants (Musa acuminata) are reported. Upon absorption of light energy all studied phenylphenalenones sensitise the production of singlet oxygen in polar and non-polar media. Antifungal activity of these compounds towards Fusarium oxysporum is enhanced in the presence of light. These results, together with the correlation of IC50 values under illumination with the quantum yield of singlet oxygen production and the enhancing effect of D2O on the antifungal activity, suggest the intermediacy of singlet oxygen produced by electronic excitation of the phenylphenalenone phytoalexins.
Subject(s)
Antifungal Agents/pharmacology , Plant Extracts/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/radiation effects , Fruit/chemistry , Fusarium/radiation effects , Light , Molecular Structure , Photochemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/radiation effects , Sesquiterpenes , Singlet Oxygen/chemistry , Terpenes , PhytoalexinsABSTRACT
Two antifungal phenyl-phenalenone phytoalexins isolated from the banana plant (Musa acuminata) elicited with the fungus Fusarium oxysporum, together with a methoxy derivative of one of them and two epoxide precursors of their chemical synthesis, were tested for leishmanicidal activity on Leishmania donovani promastigotes and L. infantum amastigotes. Drugs inhibited proliferation of both forms of the parasite with a 50% lethal concentration range between 10.3 and 68.7 micro g/ml. Their lethal mechanism was found linked to the respiratory chain by a systematic approach, including electron microscopy, measurement of the oxygen consumption rate on digitonin-permeabilized promastigotes, and enzymatic assays on a mitochondrial enriched fraction. Whereas the whole set of compounds inhibited the activity of fumarate reductase in the mitochondrial fraction (50% effective concentration [EC(50)] between 33.3 and 78.8 micro g/ml) and on purified enzyme (EC(50) = 53.3 to 115 micro g/ml), inhibition for succinate dehydrogenase was only observed for the two phytoalexins with the highest leishmanicidal activity: anigorufone and its natural analogue 2-methoxy-9-phenyl-phenalen-1-one (EC(50) = 33.5 and 59.6 micro g/ml, respectively). These results provided a new structural motif, phenyl-phenalenone, as a new lead for leishmanicidal activity, and support the use of plant extracts enriched in antifungal phytoalexins, synthesized under fungal challenge, as a more rational and effective strategy to screen for new plant leishmanicidal drugs.
Subject(s)
Antiprotozoal Agents/pharmacology , Fungi , Leishmania donovani/drug effects , Musa/metabolism , Musa/microbiology , Phenalenes/pharmacology , Adenosine Triphosphate/metabolism , Animals , Cell Division/drug effects , Cell Line , Cell Membrane/drug effects , Cell Membrane/ultrastructure , Cell Survival/drug effects , Kinetics , Leishmania donovani/ultrastructure , Luminescent Measurements , Macrophages/drug effects , Mice , Microscopy, Electron , NADPH-Ferrihemoprotein Reductase/antagonists & inhibitors , NADPH-Ferrihemoprotein Reductase/metabolism , Oxygen Consumption/drug effects , Succinate Dehydrogenase/antagonists & inhibitors , Succinate Dehydrogenase/metabolismABSTRACT
The pentacyclic triterpenes rhoiptelenol and rhoiptelenone have been isolated from Sideritis macrostachya. Rhoiptelenone is a new natural compound, whose structure has been determined as D:B-friedo-urs-5-en-3-one. The 1H and 13C NMR spectra of rhoiptelenol, rhoiptelenol acetate and glutinol have been reassigned. The natural occurrence of the D:B-friedo-ursene and D:B-friedo-oleanene derivatives has been examined.
Subject(s)
Sideritis/chemistry , Triterpenes/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Triterpenes/isolation & purificationABSTRACT
The known diterpenes rosmanol (3), rosmaquinone (4), 7-methoxyrosmanol (5), 7-ethoxyrosmanol (6), galdosol (7), and epirosmanol (8) have been obtained by partial synthesis from carnosol (2), an abundant natural product present in Salvia species. The physical and spectroscopic data of these semisynthetic diterpenes were identical to those of authentic natural samples and with data reported in the literature. These abietane diterpenes have very interesting biological activities and are present in the genus Salviain low quantities; thus, the semisynthetic approach described here represents an efficient alternative method to obtain these compounds. Additionally, the known diterpene 16-hydroxyrosmanol (10) and a new aromatic diterpene 11 were obtained from 16-hydroxycarnosol (9) by reaction with Ph3P/NBS in CH2Cl2. The structure of the new compound 11 was established from its spectroscopic data as 12,16-epoxycarnosol.
