Phytotoxicity of Schiekia timida Seed Extracts, a Mixture of Phenylphenalenones.

Phenylphenalenones, metabolites found in Schiekia timida (Haemodoraceae), are a class of specialized metabolites with many biological activities, being phytoalexins in banana plants. In the constant search to solve the problem of glyphosate and to avoid resistance to commercial herbicides, this work aimed to investigate the phytotoxic effect of the methanolic extract of S. timida seeds. The chemical composition of the seed extract was directly investigated by NMR and UPLC-QToF MS and the pre- and post-emergence phytotoxic effect on a eudicotyledonous model (Lactuca sativa) and a monocotyledonous model (Allium cepa) was evaluated through germination and seedling growth tests. Three concentrations of the extract (0.25, 0.50, and 1.00 mg/mL) were prepared, and four replicates for each of them were analyzed. Three major phenylphenalenones were identified by NMR spectroscopy: 4-hydroxy-anigorufone, methoxyanigorufone, and anigorufone, two of those reported for the first time in S. timida. The presence of seven other phenylphenalenones was suggested by the LC-MS analyses. The phenylphenalenone mixture did not affect the germination rate, but impaired radicle and hypocotyl growth on both models. The effect in the monocotyledonous model was statistically similar to glyphosate in the lowest concentration (0.25 mg/mL). Therefore, although more research on this topic is required to probe this first report, this investigation suggests for the first time that phenylphenalenone compounds may be post-emergence herbicides.

A novel turn-on fluorescent probe for selective sensing and imaging of glutathione in live cells and organisms.

We synthesized six 1-oxo-1H-phenalene-2,3-dicarbonitrile (OPD)-based probes with various leaving groups using an arylthioether linker and for the first time identified the probe O-NH2 capable of highly selective detection of glutathione over cysteine/homocysteine in vitro and in vivo based on an aromatic nuclear substitution reaction (SNAr) mechanism. The fluorescence of the probe O-NH2 was quenched because of the photoinduced electron transfer (PET) process, but switched on by a glutathione-triggered specific recognition reaction between the probe O-NH2 and glutathione. The recognition mechanism for glutathione was explored and verified by theoretical calculations and ESI-MS analysis. Using O-NH2 as the probe, the GSH fluorescence images were demonstrated in HeLa cells and the intracellular GSH levels in different imatinib-resistant K562 tumor cells were firstly determined. Further, O-NH2 was utilized to detect glutathione in D. magna and zebrafish embryos. The combined results indicate that O-NH2 can be applied as an effective tool for detecting glutathione in biological investigations.

In vitro activity of 1H-phenalen-1-one derivatives against Acanthamoeba castellanii Neff and their mechanisms of cell death.

Acanthamoeba is an opportunistic pathogen which is the causal agent of a sight-threatening ulceration of the cornea known as Acanthamoeba keratitis (AK) and, more rarely, an infection of the central nervous system called "granulomatous amoebic encephalitis" (GAE). The symptoms of AK are non-specific, and so it can be misdiagnosed as a viral, bacterial, or fungal keratitis. Furthermore, current therapeutic measures against AK are arduous, and show limited efficacy against the cyst stage of Acanthamoeba. 1H-Phenalen-1-one (PH) containing compounds have been isolated from plants and fungi, where they play a crucial role in the defense mechanism of plants. Natural as well as synthetic PHs exhibit a diverse range of biological activities against fungi, protozoan parasites or human cancer cells. New synthetic PHs have been tested in this study and they show a potential activity against this protozoa.

Synthesis and in vitro antiprotozoal evaluation of substituted phenalenone analogues.

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.

Barakol contents in fresh and cooked Senna siamea leaves.

Senna siamea (Lam.) Irwin and Barneby is a medicinal plant popularly used in Thailand. Young leaves and/or young flowers of this plant have been consumed by Thai people as a Khi Lek curry for a long time. The fresh young leaves and flowers are boiled with water 2-3 times to get rid of the bitterness and the boiled mush is used for curry cooking. Barakol, a major constituent of Senna siamea leaves was analyzed for its content in the fresh young leaves, the boiled leaves and the boiled filtrates by a high-performance thin-layer chromatographic method. Fresh young leaves of S. siamea contained 0.4035% w/w barakol. The amount of barakol in the first and second boiled filtrates were 0.2052 and 0.1079% fresh weight, while the first and second boiled leaves samples were 0.1408 and 0.0414% fresh weight, respectively. The results show the process of preparation of Khi Lek curry by boiling S. siamea young leaves twice with water reduced barakol content up to 90% and the content of barakol in boiled leaves used for curry has much less tendency to cause liver toxicity. This may explain the reason why Thai Khi Lek curry has not caused hepatotoxicity, unlike S. siamea leaves consumed as a powdered capsule.

Barakol-induced apoptosis in P19 cells through generation of reactive oxygen species and activation of caspase-9.

ETHNOPHARMACOLOGICAL RELEVANCE: Barakol, an anxiolytic agent isolated from Senna siamea leaves which has been traditionally used for producing natural sleep, has been described as toxic to patients. AIM OF THE STUDY: The aim of current study was to investigate the molecular mechanism of barakol-induced toxicity in mouse embryonal carcinoma P19 cell model. MATERIALS AND METHODS: XTT assay was used to determine cell viability in P19 cells treated with barakol. Apoptotic cells were detected by Hoechst 33342 staining. Intracellular reactive oxygen species (ROS) generation was analyzed by flow cytometry using a fluorescent dye, DCFH-DA. Detection of apoptotic protein expression in P19 cells was performed by Western blot analysis. Caspase-9 activity was measured using a fluorescent immunosorbent enzyme assay kit. RESULTS: Treatment with barakol decreased cell viability in a concentration- and time-dependent manner with an IC(50) value of 1.5mM in 24-h treated cells. A Hoechst 33342 assay revealed that barakol cytotoxicity was due to a significant increase in the number of apoptotic cells. Different scavengers to characterize ROS were utilized and revealed that hydroxyl radicals played a major role in ROS-induced apoptosis in barakol-treated cells. Western blot analysis demonstrated that barakol-induced apoptosis was mediated by the increase in expression ratio of Bax/Bcl-2. Furthermore, increase in caspase-9 activity after exposure to barakol for 24h was also observed. Pretreatment of cells with N-acetyl-l-cysteine (NAC) attenuated intracellular ROS generation, the Bax/Bcl-2 protein expression, and apoptosis. CONCLUSIONS: The mechanism of barakol-mediated toxicity in P19 cells is mainly associated with the ROS generation, followed by the imbalance of the Bax/Bcl-2 ratio, and caspase-9 activation leading to apoptotic cell death. Pretreatment of cells with NAC could antagonize the toxicity produced by barakol.

Bacillisporins D and E, new oxyphenalenone dimers from Talaromyces bacillisporus.

The oligophenalenone dimer duclauxin and two new analogues, bacillisporins D and E, were isolated from the fungus TALAROMYCES BACILLISPORUS in addition to the previously reported bacillisporins A, B and C. Structures were established by spectroscopic studies. Duclauxin and bacillisporins A, B, C and E were evaluated for cytotoxicity against three human cancer cell lines. Bacillisporin A was strongly active against MCF-7 and NCI-H460 and moderately active against SF-268 while bacillisporins B, C and duclauxin were moderately active against all three cell lines.