Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition.

Nocuolin A (1), an oxadiazine, was isolated from the cyanobacterium Nostoc sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate (2) and 4-{3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropoxy}-4-oxobutanoic acid (3), were synthesised. The chemical structures of these two compounds were elucidated by a combination of NMR and MS analysis. Compound 3 showed cytotoxicity against the ACHN (0.73 ± 0.10 µM) and Hepa-1c1c7 (0.91 ± 0.08 µM) tumour cell lines. Similarly, compound 3 significantly decreased cathepsin B activity in ACHN and Hepa-1c1c7 tumour cell lines at concentrations of 1.52 ± 0.13 nM and 1.76 ± 0.24 nM, respectively. In addition, compound 3 showed no in vivo toxicity in a murine model treated with a dose of 4 mg/kg body weight.

Identification of TRPV1 Ion Channels Agonists of Tropaeolum tuberosum in Human Skin Keratinocytes.

Tropaeolum tuberosum, commonly known as Mashua, is an herbal remedy used in traditional Andean medicine for the relief of kidney and bladder pain, as well as contusions. This study aimed to evaluate the fractions and isolated compounds from T. tuberosum with analgesic activity mediated by the transient receptor potential vanilloid-1 receptor. A bioguided phytochemical analysis based on NMR/MS was performed to identify the compounds of the n-heptane fractions from samples of purple tubers of T. tuberosum. The transient receptor potential vanilloid-1 agonist and antagonist activity were assessed through the measurement of intracellular Ca2+ in HEK001 cells. The chemical structure determination led to the identification of two alkamides: N-(2-hydroxyethyl)-7Z,10Z,13Z,16Z-docosatetraenamide (1: ) and N-oleoyldopamine (2: ). Both compounds induced increased intracellular calcium flow with IC50 values of 3.2 nM and 7.9 nM, respectively, thus activating the transient receptor potential vanilloid-1 receptor. Our research is the first report to show that these two compounds isolated from T. tuberosum can act as agonists of the transient receptor potential vanilloid-1 receptor, providing scientific evidence for the traditional use of this species in pain relief.

Molecular Targets Involved in the Neuroprotection Mediated by Terpenoids.

Natural products and their derivatives represent the most consistently successful source of drug leads. Terpenoids, a structurally diverse group, are secondary metabolites widely distributed in nature, endowed with a wide range of biological activities such as antibacterial, anti-inflammatory, antitumoral, or neuroprotective effects, which consolidate their therapeutic value. During the last decades, and taking into consideration the prevalence of aging-related diseases, research activity into the neuroprotective effects of these types of compounds has increased enormously. Several signaling pathways involved in neuroprotection are targets of their mechanism of action and mediate their pleiotropic protective activity in neuronal cell damage. In the present review, molecular basis of the neuroprotection exerted by terpenoids is presented, focusing on preclinical evidence of the therapeutic potential of diterpenoids and triterpenoids on neurodegenerative disorders. By acting on diverse mechanisms simultaneously, terpenoids have been emphasized as promising multitarget agents.

Expedited Discharge from an Academic Emergency Department: A Pilot Program.

BACKGROUND: As the numbers of emergency department (ED) visits and inpatient admissions continue to increase, there is growing interest in alternatives to inpatient hospitalization. OBJECTIVE: Our aim was to investigate a novel approach to expediting discharges from the ED with multidisciplinary discharge services to prevent an avoidable admission into the hospital. METHODS: This pilot study was conducted at a large urban tertiary-care ED in 2016. All patients presenting to the ED with planned inpatient or observation admission were considered for discharge with enhanced discharge planning services. The patients selected, discharge diagnoses, and outcomes were analyzed by descriptive statistics. This study was approved by the study site's Institutional Review Board, including waiver of patient consent. RESULTS: During the pilot period, 57 out of 143 (40%) selected patients with planned admission were discharged with enhanced discharge planning services. Median ED length of stay was 17.2 h and mean patient age was 73 years old. Of these patients, 7 (12%) returned within 72 h and 4 (0.07%) were subsequently admitted to the hospital. CONCLUSIONS: In this pilot study, a novel approach to expediting discharges from the ED with multidisciplinary discharge services was feasible and resulted in fewer admissions to the hospital.

The preventive and therapeutic consumption of meat enriched with carob fruit extract, rich in phenolic compounds, improves colonic antioxidant status in late-stage T2DM rats.

Oxidative stress is prevalent in Type 2 Diabetes Mellitus (T2DM) and has been associated with high meat consumption. Carob Fruit Extract (CFE) contains phenolic compounds, making it a suitable functional ingredient. Current study aims to evaluate the effect of CFE-enriched meat (CFE-meat) consumption on the antioxidant status of proximal and distal colon, and its relationship with fecal phenolic compounds in late-stage T2DM rats. Three groups of eight rats were studied: 1) D, fed control-meat; 2) ED, fed CFE-meat since the beginning of the study; 3) DE, fed CFE-meat after confirming T2DM. CFE-meat consumption reduces colonic oxidative stress mainly in the proximal section and helps to ameliorate glutathione metabolism and antioxidant score. Difference between ED and DE groups were associated with colon homeostasis and T2DM progression suggesting greater fermentation but lower absorption in the DE group. CFE appears as a promising tool to improve the antioxidant status observed in late-stage T2DM.

Maca (Lepidium meyenii Walp.) inhibits HIV-1 infection through the activity of thiadiazole alkaloids in viral integration.

ETHNOPHARMACOLOGY RELEVANCE: Lepidium meyenii Walp. (maca) has been traditionally used for centuries in the Central Andes region both as food and as medicine. In the last decades, its fertility enhancer properties have gained importance, with the majority of the scientific literature related to this topic. However, other traditional uses are less known as metabolic or infectious diseases. AIM OF THE STUDY: The main purpose of this study is to investigate the anti-infectious activity of L. meyenii, specifically in HIV-1 infection. There are previous reports of the transcriptional related activity of L. meyenii extracts in human T lymphocytes via transcription factors as NF-κB. Since T lymphocytes are the main target of HIV-1 infection and NF-κB is strongly involved in HIV-1 transcription, L. meyenii could display antiviral activity. MATERIAL AND METHODS: Chromatography and spectroscopy techniques were used to isolate and identify the compounds in the active extracts. An antiviral assay system based on recombinant viruses was used to evaluate the anti-HIV activity. Cell toxicity was tested for all the extracts and compounds. Viral entry was studied using VSV-HIV chimera viruses and reverse transcription and viral integration were studied by qPCR of viral DNA in infected cells. Finally, viral transcription was studied in primary lymphocytes transfected with HIV-1 or NF-κB luciferase reporter plasmids. RESULTS: n-Hexane extracts of purple maca displayed anti-HIV activity in an in vitro assay. A bioassay-guided fractionation led to the identification of three thiadiazole alkaloids with antiviral activity. All the compounds were able to inhibit HIV infection of MT-2 cell lines and primary lymphocytes (PBMCs) with IC50 values in the low micromolar range. The mechanism of action differs between the three compounds: one of them showed activity on viral entry, and all the three compounds inhibited viral integration at low concentrations. Remarkably, none of the compounds inhibited reverse transcription or viral transcription. CONCLUSIONS: n-Hexane extracts of the purple ecotype of L. meyenii inhibit HIV-1 infection in vitro and three active thiadiazole alkaloids were isolated acting mainly on viral integration and viral entry.

Novel 1,2,4-oxadiazole compounds as PPAR-α ligand agonists: a new strategy for the design of antitumour compounds.

Modulation of PPAR-α by natural ligands is a novel strategy for the development of anticancer therapies. A series of 16 compounds based on the structure of 3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole (natural compound) with antitumour potential were designed and synthesised. The cytotoxicity and PPAR agonist activity of these synthetic 1,2,4-oxadiazoles were evaluated in the A-498 and DU 145 tumour cell lines. Preliminary biological evaluation showed that most of these synthetic 1,2,4-oxadiazoles are less cytotoxic (sulforhodamine B assay) than the positive control WY-14643. Regarding the PPAR-α modulation, compound 16 was the most active, with EC50 = 0.23-0.83 µM (PPAR-α). Additionally, compound 16 had a similar activity to the natural compound (EC50 = 0.18-0.77 µM) and was less toxic in the RPTEC and WPMY-1 cell lines (non-tumour cells) (CC50 = 81.66-92.67 µM) than the natural compound. Looking at the link between chemical structure and activity, our study demonstrates that changes to the natural 1,2,4-oxadiazole at the level of the thiophenyl residue can lead to new agonists of PPAR-α with promising anti-tumour activity.

Antitumoral activity of 1,2,4-oxadiazoles compounds isolated from the Neowerdermannia vorwerkii in liver and colon human cancer cells.

Two unknown 1,2,4-oxadiazoles (3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) and one known 1,2,4-oxadiazole (5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) were isolated from tubers of Neowerdermannia vorwerkii, collected from the San Juan Huancollo, Ingavi province, La Paz, Bolivia. The chemical structures of these compounds were elucidated through NMR and HRMS spectroscopic analyses. All compounds showed apoptotic capacity against the SK-HEP-1 and Caco-2 tumour cells. 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2, 4-oxadiazole showed slight apoptotic capacities, with an IC50 between 17.46 ± 0.75 to 15.91 ± 0.62 µM and 39.29 ± 0.98 to 34.81 ± 0.70 µM, respectively. 3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole showed a higher apoptotic capacity with an IC50 in the range of 0.98 ± 0.11 to 0.76 ± 0.03 µM, similar to that of the positive control (Dimethylenastron).

Anti-inflammatory properties of Neowerdermannia vorwerkii Fric 'Achacana' used in treating stomach-related ailments.

ETHNO-PHARMACOLOGICAL RELEVANCE: The tuber of Neowerdermannia vorwerkii commonly known as 'Achacana' is used as an infusion in Andean countries to treat various gastrointestinal ailments, kidney and liver diseases. AIM OF THE STUDY: This study determined the anti-inflammatory activity of the aqueous extract from Neowerdermannia vorwerkii and identified the compounds related to this activity. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Neowerdermannia vorwerkii was carried out, selecting the sub-extracts and fractions depending on their anti-inflammatory activity in the Hs 738.St/Int, Hs 746T and NCI-N87 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3-(pyridin-3-yl)-5-(tiophen-3-yl)-1,2,4-oxadiazole (1), 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (2) and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (3). Regarding their anti-inflammatory activity, the three compounds inhibited the production of cytokines (IL-1ß, IL-6 and TNF-α), however, compound 1 was the most active, with an IC50 of 0.87 µM in all cell lines. CONCLUSION: In the present study, the anti-inflammatory activity of the aqueous extract of Neowerdermannia vorwerkii was tested and analysed, following the isolation of three 1,2,4-oxadiazoles type compounds with similar pharmacological properties.

Wound healing, anti-inflammatory and anti-melanogenic activities of ursane-type triterpenes from Semialarium mexicanum (Miers) Mennega.

ETHNO-PHARMACOLOGICAL RELEVANCE: The bark of Semialarium mexicanum commonly known as 'Cancerina' is used as an infusion in Central America and Mexico to treat various wound infections, as well as skin and vaginal ulcers. AIM OF THE STUDY: This study aimed to determine the wound healing, anti-inflammatory and anti-melanogenic activities of the aqueous extract of Semialarium mexicanum and to identify the compounds related to these activities. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Semialarium mexicanum was carried out, selecting the sub-extracts and fractions depending on their wound healing, anti-inflammatory and anti-melanogenic activities in the RAW 264.7, NIH/3T3 and B16-F10 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3ß)-3-Hydroxy-urs-12-en-28-oic acid (1), (3ß)-Urs-12-ene-3,28-diol (2) and (2α, 19α)-2,19-Dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Regarding the anti-inflammatory activity, the three compounds inhibited the production of NF-κB and NO, however, compound 3 was the most active with IC50 values of 8.15-8.19 µM and 8.94-9.14 µM, respectively, in all cell lines. The anti-melanogenic activity of these compounds was evaluated by the inhibition of tyrosinase and melanin in the B16-F10 cell line. The three compounds showed anti-melanogenic activity, however, compound 3 was the most active with an IC50 of 8.03 µM for the inhibition of tyrosinase production, and an IC50 of 8.53 µM for the inhibition of melanin production. Finally, concerning the wound healing activity, the three compounds presented proliferative activity in all the tested cell lines, however, compound 3 showed higher cell proliferation percentages than compounds 1 and 2 (88.89-89.60% compared to 64.92-65.71% and 71.53-71.99%, respectively). CONCLUSION: The wound healing, anti-inflammatory and anti-melanogenic activity of the aqueous extract of Semialarium mexicanum was tested and analysed in the present study, after having isolated three ursane-type triterpenes.

Inhibition of melanin production and tyrosinase activity by flavonoids isolated from Loranthus acutifolius.

Activity-guided fractionations of leaves and stems from Loranthus acutifolius led to the isolation of 2',4',6-trimethoxyflavone (1), 3',4',5-trihydroxy-6,7,8-trimethoxyflavone (2), 2'4'-dihydroxy-6'-methoxy-chalcone (3) and 4',5-dihydroxy-6,7,8-trimethoxyflavone (4). The potential for inhibition against melanin production and tyrosinase activity of these 4 compounds was tested in B16-F10 cells. 2',4',6-trimethoxyflavone, 3',4',5-trihydroxy-6,7,8-trimethoxyflavone, 2'4'-dihydroxy-6'-methoxy-chalcone and 4',5-dihydroxy-6,7,8-trimethoxyflavone showed an inhibitory activity of melanin production with IC50 of 3.6 ± 0.05 µM, 8.1 ± 0.05 µM, 1.6 ± 0.03 µM and 6.5 ± 0.05 µM, respectively. In addition, 2',4',6-trimethoxyflavone, 3',4',5-trihydroxy-6,7,8-trimethoxyflavone, 2'4'-dihydroxy-6'-methoxy-chalcone and 4',5-dihydroxy-6,7,8-trimethoxyflavone were able to inhibit tyrosinase activity with IC50 of 4.0 ± 0.03 µM, 11.3 ± 0.05 µM, 5.7 ± 0.02 µM and 8.6 ± 0.04 µM, respectively. This is the first time that these compounds are reported in the L. acutifolius species showing anti-melanogenic activities.

Antimicrobial compounds isolated from Tropaeolum tuberosum.

Activity-guided fractionations of black tubers of Tropaeolum tuberosum led to the isolation of 3-[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl] benzonitrile (1) and [3,5-Bis (1,1-dimethylethyl)-4-hydroxyphenyl] ethenylidene] bis-phosphonic acid tetraethyl ester (2). Compounds 1 and 2 showed an antibacterial effect against almost all the strains assayed, especially compound 2, showing the same inhibition potential for Enterococcus faecalis and Salmonella enteritidis as the ampicillin (MIC = 1.5 µM) and a better potential than chloramphenicol which has a MIC of 3.5 µM. In addition, compounds 1 and 2 showed a relevant antifungal inhibition against Candida tropicalis with MICs of 100 µM and 50 µM, and against Saccharomyces kudriavzevii with MICs of 25 µM and 1.5 µM. This is in comparison to fluconazole which had MICs of 150 µM (against Candida tropicalis) and 3.5 µM (against Saccharomyces kudriavzevii). This is the first time that compounds 1 and 2 are reported as showing antimicrobial activities.

Hydroalcoholic extract of Tagetes minuta L. inhibits inflammatory bowel disease through the activity of pheophytins on the NF-κB signalling pathway.

ETHNO-PHARMACOLOGICAL RELEVANCE: Species of the genus Tagetes are well known for their anti-inflammatory properties. Tagetes minuta "Huacatay" is an endemic species of South America that has been used in traditional medicine since ancient times as a remedy for stomach and intestinal discomfort. AIM OF THE STUDY: The aim of this study is to investigate the anti-inflammatory activity of the aqueous and hydroalcoholic extracts of the Huacatay, identifying the compounds responsible for this activity. MATERIALS AND METHODS: Anti-inflammatory activity of the compounds, fractions and extracts was evaluated in Hs 746T (stomach), HIEC-6 (intestine) and THP-1 (monocytes peripheral blood) cells by measuring their inhibitory capacity against the NF-κB production. RESULTS: Aqueous and hydroalcoholic extracts of Tagetes minuta displayed anti-inflammatory activity in vitro, the hydroalcoholic extract being the most active (IC50 between 59.72 and 66.42 µg/mL) in all cell lines. Bio-guided hydroalcoholic extract fractionation led to the isolation and characterisation of two pheophytins, pheophytin a (1) and 132-hydroxy pheophytin a (2). Both compounds inhibited the production of NF-κB with IC50 values in the low micromolar range, with an IC50 between 12.32 and 16.01 µM for compound 1 and 7.91-9.87 µM for compound 2. CONCLUSIONS: The two pheophytins isolated in this study inhibit the production of NF-κB, thus showing that the traditional anti-inflammatory use of Tagetes minuta can be proved through pharmacological assays. This contributes to understanding the anti-inflammatory activity of the Huacatay extracts and their use in the treatment of stomach and intestinal discomfort.

Anti-inflammatory activity of glycolipids isolated from cyanobacterium Nodularia harveyana.

Activity-guided fractionations from the freshwater cyanobacterium Nodularia harveyana led to the isolation of two monogalactosyldiacylglycerols (MGDG), two digalactosyldiacylglycerols (DGDG), two monoglucosyldiacylglycerols (MGlcDG) and 1-(O-hexose)-3,25-hexacosanediol (HG). Structures were elucidated by a combination of 1D and 2D NMR analysis, HRMS and GC-MS. The potential for inhibition against TNF-α and NF-κB production of these seven compounds was tested in THP-1 cells. All compounds showed activity, but compound 7 showed higher inhibitory activity of TNF-α and NF-κB, with IC50 of 4.88 ± 0.13 and 3.64 ± 0.45 µM, respectively.

Local/traditional uses, secondary metabolites and biological activities of Mashua (Tropaeolum tuberosum Ruíz & Pavón).

ETHNOPHARMACOLOGICAL RELEVANCE: Tropaeolum tuberosum Ruíz & Pavón (Tropaeolaceae). Sim (commonly called Mashua) is an indigenous plant that has medicinal values for various ethnic groups of the regions of the Andes mountain range of South America, which use it for the treatment of diseases venereal, lung and skin; for the healing of internal and external wounds; and as an analgesic for kidney and bladder pain. AIM OF THE REVIEW: We critically summarised the current evidence on the botanic characterisation and distribution, ethnopharmacology, secondary metabolites, pharmacological activities, qualitative and quantitative analysis, and toxicology of T. tuberosum. MATERIALS AND METHODS: The relevant information on T. tuberosum was gathered from worldwide accepted scientific databases via electronic search (Google scholar, Elsevier, SciFinder, ScienceDirect, PubMed, SpringerLink, Web of Science, Scopus, Wiley Online, Mendeley, Scielo and Dialnet electronic databases). Information was also obtained from the literature and books as well as PhD and MSc dissertations. Plant names were validated by 'The Plant List' (www.theplantlist.org). RESULTS: T. tuberosum has diverse uses in local and popular medicine, specifically for relieving pain and infections in humans. Regarding its biological activities, polar extracts (aqueous, hydroalcoholic) and isolated compounds from the tubers have exhibited a wide range of in vitro and in vivo pharmacological effects, including antibacterial, antioxidant, anti-inflammatory activities. Quantitative analysis (e.g., NMR, HPLC, GC-MS) indicated the presence of a set of secondary metabolites, including hydroxybenzoic acids, tannins, flavanols, anthocyanins, glucosinolates, isothiocyanates, phytosterols, fatty acids and alkamides in the tubers of T. tuberosum. Likewise, glucosinolates have been identified in the seeds and isothiocyanates have been detected in leaves, flowers and seeds. CONCLUSIONS: T. tuberosum has been tested for various biological activities and the extracts (tubers in particular) demonstrated a promising potential as an antibacterial, antioxidant, anti-inflammatory and inhibitors of benign prostatic hyperplasia. A lack of alignment between the ethno-medicinal uses and existing biological screenings was observed, indicating the need to explore its potential for the treatment against respiratory affections, urinary affections and blood diseases. Likewise, it is necessary to analyse deeply the relationship that exists between the different tuber colours of T. tuberosum and its use for the treatment of certain diseases. Validation of clinical studies of the antibacterial, antioxidant/anti-inflammatory, anti-spermatogenic activities and as inhibitors of benign prostatic hyperplasia is required. Moreover, studies on the toxicity, bioavailability, and pharmacokinetics, in addition to clinical trials, are indispensable for assessing the safety and efficacy of the active metabolites or extracts obtained from T. tuberosum. Other areas that need investigation are the development of future applications based on their active metabolites, such as neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease). Finally, the work purposes to motivate other research groups to carry out a series of scientific studies that can fill the gaps that exist with respect to Mashua properties, and thus be able to change the focus of T. tuberosum (Mashua) that currently has in the consumer society.

Alkaloids isolated from Tropaeolum tuberosum with cytotoxic activity and apoptotic capacity in tumour cell lines.

Two alkaloids were isolated and identified for the first time in the black tubers of Tropaeolum tuberosum, collected from the Titicani-Taca, Ingavi province in La Paz, Bolivia. Their structures were elucidated by extensive NMR and MS spectroscopic analyses. The isolated compounds were evaluated for their cytotoxicity and apoptotic capacity against four human cancer cell lines. 2-Benzyl-3-thioxohexahydropyrrolo[1,2-c]imidazole-1-one (1) showed slight cytotoxic activity against all the cancer cell lines which were tested, with IC50 values ranging from 27.45 ± 0.80 to 31.07 ± 0.87 µM. Moreover, N-(4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl) acetamide (2) showed significant anti-cancer potential, with IC50 values between 1.26 ± 0.57 µM and 1.37 ± 0.09 µM against all human cancer cell lines which were tested. Treatment of tumour cell lines with the compounds caused an increase in the apoptotic rate of these cells, observing that compound 2 presented an apoptotic effect which was double with respect to the control (Dimethylenastron).

Synthesis and biological screening of a library of macamides as TNF-α inhibitors.

Thirty-five macamide analogues were synthesised by modifying the initial molecular structure. The resulting structures were confirmed using NMR and MS. Cytotoxicity and the anti-inflammatory activity of these synthetic macamides were evaluated in the THP-1 cell line. Preliminary biological evaluation indicated that most of these synthetic macamides did not present cytotoxicity (MTT assay) in the tested cell line with respect to the control (actinomycin D). Regarding the anti-inflammatory activity, several analogues had a greater potential for inhibition of TNF-α than natural macamides. Synthetic macamide 4a was the most active (IC50 = 0.009 ± 0.001 µM) compared to the C87 (control). Through looking at the link between the chemical structure and the activity, our study proves that changes made to natural macamides at the level of the alkyl chain, the benzyl position, the amide bond, and the addition of two methyl groups to the aromatic ring (meta position) lead us to obtaining new macamides with greater anti-inflammatory activity.

Antitumoral potential of carbamidocyclophanes and carbamidocylindrofridin A isolated from the cyanobacterium Cylindrospermum stagnale BEA 0605B.

Three carbamidocyclophanes, A, F and V, and carbamidocylindrofridin A were isolated from the cultured freshwater cyanobacterium Cylindrospermum stagnale, collected in the Canary Islands. The chemical structures of these compounds were elucidated through NMR, HRMS and ECD spectroscopy. The absolute configuration of carbamidocyclophane A was confirmed using X-ray-diffraction. All compounds showed apoptotic capacity against the SK-MEL-1, SK-MEL-28 and SK-MEL-31 tumour cells. Carbamidocylindrofridin A had the highest anti-tumour potential, with an IC50 of 1 ± 0.3 µM in the SK-MEL-1 cell line.

Symptoms of posttraumatic stress in parents of children with cancer: are they elevated relative to parents of healthy children?

OBJECTIVE: To examine posttraumatic stress symptoms (PTSS) in parents of children with cancer as a function of time since diagnosis, treatment status, and relapse history, and as compared to parents of healthy children. METHOD: Participants included parents of 199 children with cancer, comprising a cross-sectional sample of diagnoses and treatment phases, ranging from currently on therapy to long-term survivors, and 108 parents of healthy children obtained via acquaintance control methods. Parents completed a standardized self-report measure of PTSS. RESULTS: Within the cancer group, parental report of PTSS differed as a function of treatment status and time since diagnosis. Parents of children on active treatment endorsed similar levels of PTSS as control parents, whereas parents of children off treatment reported significantly lower levels of PTSS than did controls. Similarly, parents of long-term survivors reported significantly lower levels of PTSS than did controls, while parents of recently diagnosed children did not differ from controls on PTSS. In contrast, parents of children who had suffered a relapse reported significantly higher levels of PTSS, and were much more likely to be identified as a posttraumatic stress disorder (PTSD) case. CONCLUSIONS: As a group, parents of children with cancer did not demonstrate any evidence of increased PTSS relative to parents of healthy children. Time since diagnosis, child treatment status, and relapse history are significant determinants of parent PTSS. Only parents of children who experienced a relapse appear to be at increased risk of PTSD. The current results appear discrepant from the existing literature, and possible explanations for these discrepancies are examined.