Chemical composition, anticancer, antimicrobial activity of Aloysia citriodora Palau essential oils from four different locations in Palestine.

The primary aim of this investigation was to determine the anticancer and antimicrobial properties of essential oils (EOs) extracted from the leaves of Aloysia citriodora Palau, which were procured from four separate locations in Palestine, in addition to analyzing their chemical composition. These areas include Jericho, which has the distinction of being the lowest location on Earth, at 260 m below sea level. The EOs were acquired by hydrodistillation, and their chemical composition was examined utilizing gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentration (MIC) of EOs was assessed against six bacterial strains and one fungal species using 96-well microtiter plates. The primary components found in these oils are geranial (26.32-37.22%), neral (18.38-29.00%), and α-curcumene (7.76-16.91%) in three regions. α-Curcumene (26.94%), spathulenol (13.69%), geranial (10.79%), caryophyllene oxide (8.66%), and neral (7.59%) were found to be the most common of the 32 chemical components in the EO from Jericho. The EOs exhibited bactericidal properties, particularly against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and showed highly effective fungicidal activity. Nevertheless, the antifungal efficacy of the EO was found to surpass its antibacterial activity when administered at lower dosages. The EOs exhibited anticancer activities against melanoma cancer cells, as indicated by their IC50 values, which ranged from 4.65 to 7.96 µg/mL. A. citriodora EO possesses substantial antifungal and anticancer characteristics, rendering it appropriate for utilization in food-related contexts, hence potentially enhancing the sustainability of the food sector.

Orthopedic surgery in Palau-Current capacity, needs, and future directions.

BACKGROUND: Palau, an island nation in Micronesia, is a medically underserved area with a shortage of specialty care services. Orthopedic diagnoses in Palau remain among the three most common reasons for costly off-island medical referral. The purpose of this study was to assess Palau's current orthopedic surgery capacity and needs to inform interventions to build capacity to improve care access and quality. METHODS: Orthopedic needs and capacity assessment tools developed by global surgical outreach experts were utilized to gather information and prompt discussions with a broad range of Palau's most knowledgeable stakeholders (n = 6). Results were reported descriptively. RESULTS: Finance, community impact, governance, and professional development were the lowest-scored domains from the Capacity Assessment Tool for orthopedic surgery (CAT-os), indicating substantial opportunity to build within these domains. According to administrators (n = 3), governance and finance were the greatest capacity-building priorities, followed by professional development and partnership. Belau National Hospital (BNH) had adequate surgical infrastructure. Skin grafting, soft tissue excision/resection, infection management, and amputation were the most commonly selected procedures by stakeholders reporting orthopedic needs. CONCLUSIONS: This study utilizes a framework for orthopedic capacity-building in Palau which may inform partnership between Palau's healthcare system and orthopedic global outreach organizations with the goal of improving the quality, safety, and value of the care delivered. This demonstration of benchmarking, implementation planning, and subsequent re-evaluation lays the foundation for the understanding of capacity-building and may be applied to other medically underserved areas globally to improve access to high-quality orthopedic care.

Dental Health Utilization in Palau: Feasibility of an Oral Cancer Screening Program.

Background: Cancer is the second leading cause of death in the Western Pacific region. The prevalent tradition of chewing betel nut in Palau, an island nation in this region, is a risk factor in the development of oral cancer. Oral cancer is the fifth most common cancer in Palau, and the prognosis can be improved with early detection facilitated by visual inspection of the oral cavity by dentists. The purpose of this study is to assess the feasibility of oral cancer screening using existing dental health infrastructure in Palau. Methods: A mixed methods approach was used to explore topics related to the use of dental care resources in Palau. Primary outcome measures were collected using an electronic survey with closed- and open-ended questions addressing dental health utilization as well as barriers and facilitators to accessing dental care. Secondary measures assessed knowledge, attitudes, and beliefs about betel nut use and oral cancer. Open-ended survey questions were analyzed and coded to develop themes based in grounded theory. Results: Two hundred twenty-three surveys were completed. The mean age was 42.7 years, 80% identified as female, and most (94.3%) report having seen a dentist in Palau. Dental care is seen as important (mean score 82.3/100), and 57.9% reported it was easy to access a dentist. Themes regarding facilitators include multilevel resources and transportation. Themes regarding barriers include cost and availability of dentists/appointments. Approximately half of the respondents were current users of betel nut. Conclusion: Our results suggest facilitators are in place to promote seeking and obtaining dental care; however, existing infrastructure may not support an oral cancer screening program. These data provide important areas to address that can improve access and support the implementation of oral cancer screening through existing dental care in the future.

Volatile Compounds and Biological Activity of the Essential Oil of Aloysia citrodora Paláu: Comparison of Hydrodistillation and Microwave-Assisted Hydrodistillation.

Aromatic plants are a remarkable source of natural products. Aloysia citrodora Paláu (Verbenaceae), commonly known as lemon verbena, is a relevant source of essential oils with potential applications due to its lemony scent and bioactive properties. Studies carried out on this species have focused on the volatile composition of the essential oil obtained by Clevenger hydrodistillation (CHD), with little information available on alternative extraction methodologies or the biological properties of the oil. Therefore, this work aimed to compare the volatile composition, antioxidant activity, cytotoxicity, anti-inflammatory and antibacterial activities of the essential oil extracted by conventional hydrodistillation by Clevenger (CHD) and Microwave-Assisted Hydrodistillation (MAHD). Significant differences (p < 0.05) were observed for some compounds, including the two major ones, geranial (18.7-21.1%) and neral (15.3-16.2%). Better antioxidant activity was exhibited by the MAHD essential oil in DPPH radical scavenging and reducing power assays, while no differences were observed in the cellular antioxidant assay. The MADH essential oil also presented higher inhibition against four tumoral cell lines and exhibited lower cytotoxicity in non-tumoral cells as compared with Clevenger-extracted essential oil. In contrast, the latter showed higher anti-inflammatory activity. Both essential oils were able to inhibit the growth of eleven out of the fifteen bacterial strains tested.

Epidemiology of dermatologic disease in Palau: a cross-sectional study in the national public and community health service.

BACKGROUND: Dermatologic disease is a neglected public health challenge that disproportionately affects resource-poor settings. Globally, dermatologic disease contributes the fourth highest burden of nonfatal disability with the most acute impact in the Oceanic region, including the Republic of Palau. Efforts to address the dermatologic health inequality are hindered without the necessary epidemiologic evidence to guide health policy in the resource-poor setting of Palau. METHODS: We conducted a 4-year cross-sectional study of all Dermatology Service patients in the Belau National Hospital and outreach community health centers from 2015 to 2018. No other specialized dermatology service was available. Skin disease was classified by both diagnosis and Global Burden of Disease criteria and analyzed by age, gender, region, and surrounding Oceanic nations. RESULTS: The study enrolled 494 patients comprising 179 males and 315 females between 2015 and 2018. The most prevalent diseases were eczema (48.8%), superficial fungal infection (24.5%), and pruritus (22.7%). The neglected tropical disease of scabies was detected in four patients. Males were significantly more likely to present with cellulitis, keratinocyte carcinoma, stasis dermatitis, wounds, marine-related dermatitis, viral skin disease, tinea faciei, verruca, and xerosis and females with melasma and hyperpigmentation. CONCLUSION: This study presents the first primary epidemiologic data describing the prevalence of dermatologic disease in the Palauan adult population. The significant burden of disease in Palau compared with other Oceanic nations validates ongoing dermatology services and informs public health implications for resource allocation and disease management to achieve health equality in the resource-poor nation.

Essential oil of Aloysia citriodora Paláu and citral: sedative and anesthetic efficacy and safety in Rhamdia quelen and Ctenopharyngodon idella.

OBJECTIVE: To verify the efficacy of citral in inducing sedation and anesthesia in silver catfish (Rhamdia quelen) and grass carp (Ctenopharyngodon idella) and to assess the safety of essential oil (EO) of Aloysia citriodora and citral in inducing and maintaining anesthesia in silver catfish. STUDY DESIGN: Clinical study, randomized, parallel, multi-arm with control group in target species. ANIMALS: A total of 96 juvenile and 72 adult silver catfish and 80 juvenile grass carp were used. METHODS: Silver catfish and grass carp were exposed to different concentrations of citral, 15-675 and 15-600 µL L-1, respectively, during the maximum period of 30 minutes to verify sedation and anesthesia induction and recovery times. In addition, for anesthetic induction, silver catfish were exposed to the EO of A. citriodora and citral at 225 µL L-1 for 3.5 minutes. Then, fish were transferred to an anesthesia maintenance solution at 50 µL L-1 for 10 minutes to assess hematologic and biochemical variables at 60 minutes, 2 and 6 days after treatment. RESULTS: Citral only induced sedation from 15, 25 and 40 µLL-1 in both species. Anesthesia without mortality was induced in silver catfish at 50-600 µL L-1 and grass carp at 75-450 µL L-1. At 675 and 600 µL L-1, mortality was recorded in silver catfish and grass carp, respectively. The EO of A. citriodora and citral were safe in inducing and maintaining anesthesia in silver catfish, with mean corpuscular hemoglobin concentration being the only variable that varied in relation to time and treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Citral was effective in inducing sedation and anesthesia in both species. In addition, A. citriodora EO and citral were safe in inducing and maintaining anesthesia in silver catfish. Both agents are promising substances for the development of new drugs for fish.

An overview of the genus Aloysia Paláu (Verbenaceae): Essential oil composition, ethnobotany and biological activities.

Aloysia Paláu is an important herbal genus from the Verbenaceae family and possesses numerous remedial properties in the folk medicine of Asian, European, and, in particular, South American countries. Only a few reports have discussed some phytochemical characteristics associated with Aloysia species. Right the lack of an exhaustive report prompted us to organize this review article. Accordingly, besides the ethnobotanical knowledge of Aloysia species, their essential oil profiles, phytochemistry of the polar isolated fractions, and the relevant biological activities are discussed in detail.[Formula: see text].

Sinularamides A-G, Terpenoid-Derived Spermidine and Spermine Conjugates with Casitas B-Lineage Lymphoma Proto-Oncogene B (Cbl-b) Inhibitory Activities from a Sinularia sp. Soft Coral.

An extract of a Sinularia sp. soft coral showed inhibitory activity against the E3-ubiquitin ligase casitas B-lineage lymphoma proto-oncogene B (Cbl-b). Subsequent bioassay-guided separation of the extract provided a series of terpenoid-derived spermidine and spermine amides that were named sinularamides A-G (1-7). Compounds 1-7 represent new natural products; however, sinularamide A (1) was previously reported as a synthetic end product. The structures of sinularamides A-G (1-7) were elucidated by analysis of spectroscopic and spectrometric data from NMR, IR, and HRESIMS experiments and by comparison with literature data. All of the isolated compounds showed Cbl-b inhibitory activities with IC50 values that ranged from approximately 6.5 to 33 µM.

Novel handheld ultrasound technology to enhance non-expert screening for rheumatic heart disease in the Republic of Palau: A descriptive study.

AIM: Non-expert training in rheumatic heart disease (RHD) detection is a valuable strategy in resource-limited settings. Here we present an innovative handheld ultrasound application featuring views of correct probe position, imaging protocol and echocardiographic loops of RHD pathology versus normal, accessible during real-time scanning. METHODS: This prospective study was implemented into a pre-existing school health screening programme at an elementary school in Koror, Palau. Six learners with no prior ultrasound experience were taught a simplified screening protocol in which a mitral regurgitation jet ≥1.5 cm and/or presence of aortic insufficiency were considered a positive screen. All consented children underwent echocardiographic screening by experts with standard portable echocardiography. All positive cases and 25% of negative cases were referred for handheld scans by learners. RESULTS: A total of 26 (4.1%) children were diagnosed with borderline or definite RHD. Mean sensitivity and specificity compared to expert RHD diagnosis over all learners was 71% (standard deviation (SD) 11.3) and 92% (SD 4.9), respectively. For the three highest scanning learners, mean sensitivity was 88% (SD 4.9) and mean specificity was 90% (SD 5.7). For all definite RHD cases, sensitivity was 100% for all but one learner, who achieved sensitivity of 60%. The novel application was used in 229 of 624 (36%) of all handheld scans and 50 of 112 (45%) of expert-diagnosed positive scans, with protocol and reference features most frequently used. Utilisation of the novel application overall decreased per day of scanning per learner. CONCLUSION: Adjunctive handheld ultrasound technology may help ease non-experts into RHD screening.

Lessons from the Field: Interventions to Improve Health and Quality of Life to Address the NCD Crisis in Palau - Fostering Collaboration Across Sectors within the Government and Civil Society.

The Republic of Palau is a small island nation in the North Pacific with a population of 17,501. The islands of Palau are geographically isolated, considered rural, and medically underserved. The prevalence of non-communicable diseases (NCDs) and risk factors are very high and account for more than 75% of all deaths and disabilities. Recognizing that the high rates of NCDs are undermining health and sustainable development of the nation, Palau declared a state of health emergency due to the epidemic of NCDs. It was recognized during the development of the NCD Prevention and Control Strategic Plan of Action 2015-2020 (Palau NCD Plan) that improved collaboration between government agencies, civil society, and the private sector was needed to address this epidemic. A multi-sectoral solution was needed to address a multi-sectoral problem. Through Presidential Executive Order, the National Coordinating Mechanism for Non-Communicable Diseases (CM) was established to mobilize sufficient resources and coordinate actions to prevent and control NCDs, ensure successful implementation of the Palau NCD Plan, the World Health Organization Framework Convention on Tobacco Control, and other related plans and commitments, align such plans to national policies, ensure a health-in-all-policy approach to address health inequities, and bridge the gap between health and quality of life. Though the CM is young, improved coordination between agencies and accelerated action has taken place. Legislation was enacted that mandates 10% of alcohol and tobacco taxes be directed to NCD prevention through the Coordinating Mechanism, thus ensuring sustainability.

An Evaluation of Infertility Among Women in the Republic of Palau, 2016.

Fertility challenges are a personal and important part of a woman's reproductive health and are associated with health and lifestyle factors. Limited data exist on infertility among women in Palau. We describe the lifetime prevalence of self-reported infertility in a nationally representative sample of women in Palau and investigate the association between tobacco and/or betel nut use and infertility. During May-December 2016, a population-based survey of noncommunicable diseases was conducted in Palau using a geographically stratified random sample of households (N=2409). Men and women ≥18 years of age were chosen randomly from each selected household. The prevalence of a self-reported lifetime episode of infertility (having tried unsuccessfully to become pregnant for ≥12 months) was evaluated among 874 women aged ≥18 years by key health and lifestyle factors. Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated. Of 315 women who ever tried to become pregnant, 39.7% (95% CI: 34.2%, 45.3%) reported a lifetime episode of infertility. Prevalence was higher in women of Palauan vs other ethnicity (PR=1.6, 95% CI: 1.1, 2.3), those who self-reported poor/not good vs. excellent/ very good health status (PR=2.1, 95% CI: 1.4, 3.3), and those with a body mass index (BMI) ≥30 vs <30 (PR=1.7, 95% CI: 1.3, 2.2). Adjusted models showed that tobacco and/or betel nut users were almost twice as likely to report infertility versus non-users (PR=1.8, 95% CI: 1.3, 2.5). More research is needed to understand the infertility experiences of women in Palau and to promote lifestyle factors contributing to optimal reproductive health.

Effects of gamma radiation on the bioactivity of medicinal and aromatic plants: Mentha × piperita L., Thymus vulgaris L. and Aloysia citrodora Paláu as case studies.

Irradiation is a feasible and safe decontamination technique, being applied to several types of foods including edible and medicinal plants. The aim of this study was to evaluate the effects of different gamma radiation doses (1, 5 and 10 kGy) on the individual profile of phenolic compounds determined by HPLC-DAD-ESI/MS, and the bioactive potential (cytotoxic, virucidal, and antimicrobial activities) of Aloysia citrodora Paláu (lemon verbena), Mentha × piperita L. (peppermint) and Thymus vulgaris L. (thyme). The observed cytotoxic activity varied with the plant and with the applied dose, being higher in Thymus vulgaris irradiated with 10 kGy. The virucidal activity was also dependent on the radiation dose, but was preserved with irradiation treatment. Gamma rays had no effect on the antimicrobial activity of the studied plants. Otherwise, the effects of gamma radiation on the phenolic profile were heterogeneous, with an increase in some compounds and decrease in others, depending on the species and on the radiation dose.

Breast and Cervical Cancer Screening in Palau: Have We Improved Early Detection and Survival?

The Breast and Cervical Cancer Early Detection Program (BCCEDP) was first introduced in Palau in 1997. The program's aim is to recruit and screen women for early detection of breast and cervical cancers. An assessment of this screening program was conducted to evaluate its effectiveness, including impact on stage of diagnosis and survival time of patients diagnosed with breast and cervical cancers through both screening and clinical diagnosis. A retrospective cohort study using secondary data from 2004-2013 was conducted. There were 45 women diagnosed with breast or cervical cancer. Due to the small number of cases, a comparison of two time periods was made (2004-2008) and (2009-2013). There were more cancer cases detected through screening (26%) in the earlier time period (2004-2008), as compared to those diagnosed through screening (8%) in the later time period (2009-2013), though this difference was not statistically significant (P=.09). The proportion of breast and cervical cancers diagnosed at an earlier stage (0-3) may have decreased between the two time periods (42% to 23%, P=.3). A greater proportion of women who were diagnosed between 2004-2008 lived longer than 2 years (58%), than women who were diagnosed between 2009-2013 (39%; P=.23). The screening program has not shown improvement over the years despite the measures taken to detect the early onset of breast and cervical cancer, and survival outcomes in Palau remain poor.

The Effects of Chewing Betel Nut with Tobacco and Pre-pregnancy Obesity on Adverse Birth Outcomes Among Palauan Women.

The small Pacific Island nation of Palau has alarmingly high rates of betel nut with tobacco use and obesity among the entire population including pregnant women. This study aimed to determine the effects of betel nut with tobacco use and pre-pregnancy obesity on adverse birth outcomes. This study used retrospective cohort data on 1171 Palauan women who gave birth in Belau National Hospital in Meyuns, Republic of Palau between 2007 and 2013. The exposures of interest were pre-pregnancy obesity and reported betel nut with tobacco use during pregnancy. The primary outcomes measured were preterm birth and low birth weight among full-term infants. A significantly increased risk for low birth weight among full-term infants was demonstrated among those women who chewed betel nut with tobacco during pregnancy when other known risk factors were controlled for. Additionally, pre-pregnancy obesity was associated with a significantly increased risk for preterm birth when other known risk factors were controlled for. Both betel nut with tobacco use and pre-pregnancy obesity were associated with higher risks for adverse birth outcomes. These findings should be used to drive public health efforts in Palau, as well as in other Pacific Island nations where these studies are currently lacking.

Pharmacological and neuroprotective profile of an essential oil derived from leaves of Aloysia citrodora†Palau.

OBJECTIVES: The Jordanian 'Melissa', (Aloysia citrodora) has been poorly studied both pharmacologically and in the clinic. Essential oils (EO) derived from leaves of A. citrodora were obtained by hydrodistillation, analysed by gas chromatography-mass spectrometry (GC-MS) and were investigated for a range of neurobiological and pharmacological properties, as a basis for potential future use in drug discovery. METHODS: A selection of central nervous system (CNS) receptor-binding profiles was carried out. Antioxidant activity and ferrous iron-chelating assays were adopted, and the neuroprotective properties of A. citrodora EO assessed using hydrogen peroxide-induced and ß-amyloid-induced neurotoxicity with the CAD (Cath.-a-differentiated) neuroblastoma cell line. KEY FINDINGS: The major chemical components detected in the A. citrodora EOs, derived from dried and fresh leaves, included limonene, geranial, neral, 1, 8-cineole, curcumene, spathulenol and caryophyllene oxide, respectively. A. citrodora leaf EO inhibited [(3) H] nicotine binding to well washed rat forebrain membranes, and increased iron-chelation in vitro. A. citrodora EO displays effective antioxidant, radical-scavenging activities and significant protective properties vs both hydrogen peroxide- and ß-amyloid-induced neurotoxicity. CONCLUSIONS: A. citrodora EO displays a range of pharmacological properties worthy of further investigation to isolate the compounds responsible for the observed neuroactivities, to further analyse their mode of action and determine their clinical potential in neurodegenerative diseases.

Profile of Non-communicable Disease Risk Factors Among Young People in Palau.

BACKGROUND: Although non-communicable diseases (NCDs) have become the predominant health problems of Palauan society, there have been no comprehensive data on NCD risk factors available to develop effective control strategies. Therefore, the first Palauan national STEPwise approach to risk factor Surveillance (STEPS) was completed in mid-2013 to provide information on its adult population aged 25 to 64 years. This study aims to obtain corresponding data from the younger adults aged 18 to 24 years, who remained to be surveyed. METHODS: We conducted an epidemiological study, targeting the 18- to 24-year-old age group. A survey station and a mobile team were established to recruit voluntary participants dwelling in Koror. A slightly modified WHO STEPS instrument was used, including a structured questionnaire for behavioral risk factors, physical measurements, and blood tests. RESULTS: A total of 356 young people were recruited during the survey. In both sexes, nearly half of the participants were overweight/obese. The prevalence of hypertension was higher in men than in women (17.6% vs 1.7%). Raised blood glucose and impaired fasting glucose were observed in 3.5% and 5.2% of the total participants, respectively. About 36% of the subjects were observed to have raised levels of total cholesterol. More than 70% of the young people were current tobacco users, in terms of all kinds of tobacco products. CONCLUSIONS: The current survey, for the first time, revealed a high prevalence of NCD risk factors, especially overweight/obesity and tobacco use, among young people in Palau. This indicates that swift measures against NCDs are required even in this young age group.

Palauans who chew betel nut: social impact of oral disease.

BACKGROUND: Chewing betel nut is a tradition extending from Southeast Asia to the Pacific. Globally, betel nut is the fourth main psychotropic substance containing a stimulant, arecoline, that has a similar effect to nicotine. In Palau, there is broad acceptance of betel nut chewing. One of the largest immigrant groups in Hawaii is the Palauans. Chewing betel nut has significant social implications that make it difficult for those who engage in this practice to separate potential oral disease from the social importance. However, little is known about the social impact of oral disease from chewing betel nut on Palauans in Hawaii. AIM: The study aimed to describe the perceptions of betel-chewing Palauans in Hawaii regarding betel nut and to determine the social impact of oral disease among these individuals. METHODS: Descriptive study conducted on the island of Oahu, Hawaii with 30 adult Palauans. Data were collected using the Oral Health Impact Profile-14 to measure perceptions of social impact of oral disease on well-being. Demographic and general health information was collected. RESULTS: Participants perceived little negative social impact of oral disease on well-being. DISCUSSION: Families, peers and society exert a strong influence on the decision to chew betel nut, a known carcinogen. Participants in this study showed little concern on the impact of betel nut chewing on their oral health. They continue the habit in spite of the awareness of potential for oral disease. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurses face challenges in educating Palauans about the negative aspects of betel nut, particularly those related to oral health especially when they do not perceive problems. Nurses must be involved in the development of health policies to design and implement strategies to promote behavioural change, and to ensure clinical services that are culturally sensitive to betel nut chewers.

An assessment of non-communicable diseases, diabetes, and related risk factors in the Republic of Palau: a systems perspective.

Non-communicable diseases (NCD) have been identified as a health emergency in the US-affiliated Pacific Islands (USAPI).1 This assessment, funded by the National Institutes of Health, was conducted in the Republic of Palau and describes the burden due to selected NCD (diabetes, heart disease, hypertension, stroke, chronic kidney disease); and assesses the system of service capacity and current activities for service delivery, data collection, and reporting as well as identifying the issues that need to be addressed. There has been a 7.1% increase in the population between 2000 and 2010. Significant shifts in the age groups show declines among children and young adults under 34 years of age and increases among adult residents over 45 years of age. Findings reveal that the risk factors of poor diet, lack of physical activity, and lifestyle behaviors are associated with overweight and obesity and subsequent NCD that play a significant role in the morbidity and mortality of the population. The leading causes of death include heart disease and cancer. A 2003 community household survey was conducted and 22.4% of them reported a history of diabetes in the household. A survey among Ministry of Health employees showed that 44% of the men and 47% of the women were overweight and 46% of the men and 42% of the women were obese. Other findings show significant gaps in the system of administrative, clinical, and support services to address these NCD. Priority issues and needs for the administrative and clinical systems were identified.

Structures and potential antitumor activity of sesterterpenes from the marine sponge Hyrtios communis.

The extract of marine sponge Hyrtios communis was found to inhibit activation of the transcription factor hypoxia-inducible factor-1 (HIF-1) in T47D human breast tumor cells. Bioassay-guided isolation led to the identification of six new (1-6) and five previously reported (7-11) sesterterpene analogues and two unrelated sesterterpenes. Two new sesterterpenes, thorectidaeolide A (1) and 4-acetoxythorectidaeolide A (2), and luffariellolide (11) were among the most potent inhibitors of hypoxia (1% O2)-induced HIF-1 activation (IC50 values of 3.2, 3.5, and 3.6 µM, respectively). Luffariellolide (11) exhibited a significant level of cytotoxicity that mirrored its HIF-1 inhibitory activity. Neither compound 1, compound 2, nor any of the other less active sesterterpenes suppressed breast tumor T47D or MDA-MB-231 cell viability.

Isolation and structures of axistatins 1-3 from the Republic of Palau marine sponge Agelas axifera Hentschel .

An investigation begun in 1979 directed at the Republic of Palau marine sponge Agelas axifera Hentschel for cancer cell growth inhibitory constituents subsequently led to the isolation of three new pyrimidine diterpenes designated axistatins 1 (1), 2 (2), and 3 (3), together with the previously reported formamides 4, 5, and agelasine F (6). The structures were elucidated by analysis of 2D-NMR spectra and by HRMS. All of the isolated compounds were found to be moderate inhibitors of cancer cell growth. Axistatins 1-3 (1-3), formamide 4, and agelasine F (6) also exhibited antimicrobial activity.