US Army basic combat training alters the relationship between body mass index and per cent body fat.

INTRODUCTION/BACKGROUND: As a proxy for adiposity, body mass index (BMI) provides a practical public health metric to counter obesity-related disease trends. On an individual basis, BMI cannot distinguish fat and lean components of body composition. Further, the relationship between BMI and body composition may be altered in response to physical training. We investigated this dynamic relationship by examining the effect of US Army basic combat training (BCT) on the association between BMI and per cent body fat (%BF). METHODS: BMI and %BF were measured at the beginning (week 1) and end (week 9) of BCT in female (n=504) and male (n=965) trainees. Height and weight were obtained for BMI, and body composition was obtained by dual X-ray absorptiometry. Sensitivity and specificity of BMI-based classification were determined at two BMI thresholds (25 kg/m2 and 27.5 kg/m2). RESULTS: A progressive age-related increase in fat-free mass index (FFMI) was observed, with an inflection point at age 21 years. In soldiers aged 21+, BMI of 25.0 kg/m2 predicted 33% and 29% BF in women and 23% and 20% BF in men and BMI of 27.5 kg/m2 predicted 35% and 31% BF in women and 26% and 22% BF in men, at the start and end of BCT, respectively. Sensitivity and specificity of BMI-based classification of %BF were poor. Soldiers below BMI of 20 kg/m2 had normal instead of markedly reduced %BF, reflecting especially low FFMI. CONCLUSIONS: BCT alters the BMI-%BF relationship, with lower %BF at a given BMI by the end of BCT compared with the beginning, highlighting the unreliability of BMI to try to estimate body composition. The specific BMI threshold of 25.0 kg/m2, defined as 'overweight', is an out-of-date metric for health and performance outcomes. To the extent that %BF reflects physical readiness, these data provide evidence of a fit and capable military force at BMI greater than 25.0 kg/m2.

Thermoneutrality induces vascular dysfunction and impaired metabolic function in male Wistar rats: a new model of vascular disease.

OBJECTIVE: Cardiovascular disease is of paramount importance, yet there are few relevant rat models to investigate its pathology and explore potential therapeutics. Housing at thermoneutral temperature (30 °C) is being employed to humanize metabolic derangements in rodents. We hypothesized that housing rats in thermoneutral conditions would potentiate a high-fat diet, resulting in diabetes and dysmetabolism, and deleteriously impact vascular function, in comparison to traditional room temperature housing (22 °C). METHODS: Male Wistar rats were housed at either room temperature or thermoneutral temperatures for 16 weeks on either a low or high-fat diet. Glucose and insulin tolerance tests were conducted at the beginning and end of the study. At the study's conclusion, vasoreactivity and mitochondrial respiration of aorta and carotid were conducted. RESULTS: We observed diminished vasodilation in vessels from thermoneutral rats ( P  < 0.05), whereas high-fat diet had no effect. This effect was also observed in endothelium-denuded aorta in thermoneutral rats ( P  < 0.05). Vasoconstriction was significantly elevated in aorta of thermoneutral rats ( P  < 0.05). Diminished nitric oxide synthase activity and nitrotyrosine, and elevated glutathione activity were observed in aorta from rats housed under thermoneutral conditions, indicating a climate of lower nitric oxide and excess reactive oxygen species in aorta. Thermoneutral rat aorta also demonstrated less mitochondrial respiration with lipid substrates compared with the controls ( P  < 0.05). CONCLUSION: Our data support that thermoneutrality causes dysfunctional vasoreactivity, decreased lipid mitochondrial metabolism, and modified cellular signaling. These are critical observations as thermoneutrality is becoming prevalent for translational research models. This new model of vascular dysfunction may be useful for dissection of targetable aspects of cardiovascular disease and is a novel and necessary model of disease.

AP-2-Dependent Endocytic Recycling of the Chitin Synthase Chs3 Regulates Polarized Growth in Candida albicans.

The human fungal pathogen Candida albicans is known to require endocytosis to enable its adaptation to diverse niches and to maintain its highly polarized hyphal growth phase. While studies have identified changes in transcription leading to the synthesis and secretion of new proteins to facilitate hyphal growth, effective maintenance of hyphae also requires concomitant removal or relocalization of other cell surface molecules. The key molecules which must be removed from the cell surface, and the mechanisms behind this, have, however, remained elusive. In this study, we show that the AP-2 endocytic adaptor complex is required for the internalization of the major cell wall biosynthesis enzyme Chs3. We demonstrate that this interaction is mediated by the AP-2 mu subunit (Apm4) YXXΦ binding domain. We also show that in the absence of Chs3 recycling via AP-2, cells have abnormal cell wall composition, defective polarized cell wall deposition, and morphological defects. The study also highlights key distinctions between endocytic requirements of growth at yeast buds compared to that at hyphal tips and different requirements of AP-2 in maintaining the polarity of mannosylated proteins and ergosterol at hyphal tips. Together, our findings highlight the importance of correct cell wall deposition in cell shape maintenance and polarized growth and the key regulatory role of endocytic recycling via the AP-2 complex.IMPORTANCECandida albicans is a human commensal yeast that can cause significant morbidity and mortality in immunocompromised individuals. Within humans, C. albicans can adopt different morphologies as yeast or filamentous hyphae and can occupy different niches with distinct temperatures, pHs, CO2 levels, and nutrient availability. Both morphological switching and growth in different environments require cell surface remodelling, which involves both the addition of newly synthesized proteins as well as the removal of other proteins. In our study, we demonstrate the importance of an adaptor complex AP-2 in internalizing and recycling a specific cell surface enzyme to maintain effective polarized hyphal growth. Defects in formation of the complex or in its ability to interact directly with cargo inhibit enzyme uptake and lead to defective cell walls and aberrant hyphal morphology. Our data indicate that the AP-2 adaptor plays a central role in regulating cell surface composition in Candida.

Sepiapterin Improves Vascular Reactivity and Insulin-Stimulated Glucose in Wistar Rats.

In the vasculature, sedentary behavior leads to endothelial abnormalities, resulting in elevated cardiovascular disease risk. Endothelial nitric oxide synthase (eNOS) aberrations characterize endothelial dysfunction; eNOS also regulates mitochondrial function. We hypothesized that sepiapterin (a precursor to eNOS cofactor tetrahydrobiopterin (BH4)) supplementation would improve endothelium-dependent vascular relaxation in sedentary animals via modulation of NOS function and mitochondrial activity. Sedentary male Wistar rats were fed ad libitum for a total of 10 weeks. Sepiapterin was administered in diet during the final 5 weeks. Intraperitoneal insulin and glucose tolerance tests (IP-ITT/IP-GTT) were conducted at baseline and endpoint. Aorta was assessed for vasoreactivity and mitochondrial respiration. Insulin tolerance, determined by IP-ITT, significantly improved in rats treated with sepiapterin (p < 0.05, interaction of time and treatment). Acetylcholine- (ACh-) driven vasodilation was significantly greater in aorta from sepiapterin-treated rats as compared with control (76.4% versus 54.9% of phenylephrine contraction at 20 µM ACh, p < 0.05). Sepiapterin treatment resulted in significantly elevated state 3 (9.00 oxygen pmol/sec∗mg versus 8.17 oxygen pmol/sec∗mg, p < 0.05) and 4 (7.28 oxygen pmol/sec∗mg versus 5.86 oxygen pmol/sec∗mg, p < 0.05) aortic mitochondrial respiration with significantly lower respiratory control ratio (p < 0.05) during octanoylcarnitine-driven respiration. Vasodilation and insulin sensitivity were improved through targeting NOS via sepiapterin supplementation.

Native Language Spoken as a Risk Marker for Tooth Decay.

OBJECTIVE: The purpose of this study was to assess dmft, the number of decayed, missing (due to caries), and/ or filled primary teeth, of English-speaking and non-English speaking patients of a hospital based pediatric dental clinic under the age of 72 months to determine if native language is a risk marker for tooth decay. STUDY DESIGN: Records from an outpatient dental clinic which met the inclusion criteria were reviewed. Patient demographics and dmft score were recorded, and the patients were separated into three groups by the native language spoken by their parents: English, Spanish and all other languages. RESULTS: A total of 419 charts were assessed: 253 English-speaking, 126 Spanish-speaking, and 40 other native languages. After accounting for patient characteristics, dmft was significantly higher for the other language group than for the English-speaking (p<0.001) and Spanish-speaking groups (p<0.05), however the English-speaking and Spanish-speaking groups were not different from each other (p>0.05). CONCLUSIONS: Those patients under 72 months of age whose parents' native language is not English or Spanish, have the highest risk for increased dmft when compared to English and Spanish speaking patients. Providers should consider taking additional time to educate patients and their parents, in their native language, on the importance of routine dental care and oral hygiene.

Effect of Human Milk and its Components on Streptococcus Mutans Biofilm Formation.

OBJECTIVE: This study investigated the effects of human breast milk and its components on the nutritional aspect of the caries process due to Streptococcus mutans UA159 biofilm formation. STUDY DESIGN: Human breast milk was collected from 11 mothers during 3-9 months postpartum. To test for the effect on biofilm formation, a 16-hour culture of S. mutans was treated with dilutions of human breast milk and several major components of human breast milk, lactose, lactoferrin, IgA, and bovine casein in sterile 96-well flat bottom microtiter plates for 24 hours. The biofilms were fixed, washed, stained with crystal violet, and extracted. Absorbance was measured to evaluate biofilm growth mass. RESULTS: Dilutions 1:10-1:2,560 of the human breast milk samples increased biofilm formation by 1.5-3.8 fold compared to the control. Lactoferrin decreased biofilm formation significantly in all dilutions (average milk concentration of 3 mg/ml). Lactose had no effect at average breast milk concentrations (60 mg/ml) except at its lowest concentration (15 mg/ml) where it was increased. IgA significantly decreased biofilm formation at its highest concentration of 2,400 µg/ml (average milk concentration 600 µg/ml). Casein caused significantly increased biofilm formation at all concentrations tested above the average milk content (2.3 mg/ml). CONCLUSIONS: The results of this study demonstrate an increase in S. mutans biofilm formation by human breast milk 3-9 months post partum. Among its major components, only casein significantly increased biofilm formation among the concentrations analyzed. Lactose had no effect except at 15 mg/ml. Lactoferrin and IgA significantly decreased S. mutans biofilm formation at their highest concentrations. This information expands the current knowledge regarding the nutritional influence of breastfeeding and validates the necessity to begin an oral hygiene regimen once the first tooth erupts.

Stem cell intervention ameliorates epigallocatechin-3-gallate/lipopolysaccharide-induced hepatotoxicity in mice.

Stem cells are identified as a novel cell therapy for regenerative medicine because of their ability to differentiate into many functional cell types. We have shown earlier a new model of hepatotoxicity in mice by administering (1500 mg/kg) epigallocatechin-3-gallate (EGCG) intragastric (IG) for 5 days after a single intraperitoneal dose (6 mg/kg) of lipopolysaccharide (LPS). In this study, we aimed to study the effect of intrahepatic (IH) injection of mouse embryonic stem cells (MESCs) on the hepatotoxicity induced by EGCG/LPS in mice. Mice were administered EGCG/LPS and rested for 3 days. MESCs were obtained from American Type Culture Collection and cultured in vitro for 4 days. Stem cells were injected IH. Seven days later, a single dose of LPS (6 mg/kg) followed by daily doses of IG administration of EGCG were re-administered for 5 days. At the end of the experiment, blood samples were collected for analysis of biochemical parameters associated with liver. Results showed that the group of mice that were administered MESCs prior to EGCG/LPS showed lower levels of alanine amino transferase, alkaline phosphatase, and bilirubin, higher albumin/globulin ratio, and less remarkable histopathological lesions. Also, that group of mice showed less expression of oxidative stress biomarkers (oxidized low-density lipoprotein Ox.LDL and chemokine CXCL16), less expression of nuclear protein receptors (retinoic acid receptor and retinoid X receptor), and less expression of inflammatory biomarkers (tumor necrosis factor α and transforming growth factor ß1) compared with other groups of mice that were not given MESCs. In conclusion, MESCs can ameliorate EGCG/LPS-induced hepatotoxicity in mice.

Transfer parameters for ICRP reference animals and plants collected from a forest ecosystem.

The International Commission on Radiological Protection (ICRP) have suggested the identification of a series of terrestrial, marine and freshwater sites from which samples of each Reference animal and plant (RAP) could be systematically collected and analysed. We describe the first such study in which six of the eight terrestrial RAPs, and associated soil samples, were collected from a site located in a managed coniferous forestry plantation in north-west England. Adult life stages of species representing six of the terrestrial RAPs (Wild grass, Pine tree, Deer, Rat, Earthworm and Bee) were sampled and analysed to determine concentrations of 60 elements and gamma-emitting radionuclides. The resultant data have been used to derive concentration ratios (CR(wo-soil)) relating element/radionuclide concentrations in the RAPs to those in soil. This paper presents the first-reported transfer parameters for a number of the RAP-element combinations. Where possible, the derived CR(wo-soil) values are compared with the ICRPs-recommended values and any appreciable differences discussed.

An LC-MS based study of the metabolic profile of primaquine, an 8-aminoquinoline antiparasitic drug, with an in vitro primary human hepatocyte culture model.

The 8-aminoquinoline drug primaquine (PQ) is currently the only drug in use against the persistent malaria caused by the hypnozoite-forming strains P. vivax and P. ovale. However, despite decades of research, its complete metabolic profile is still poorly understood. In the present study, the metabolism of PQ was evaluated by incubating the drug with pooled human hepatocytes cultured in vitro as well as with recombinant cytochrome P450 (CYP) iso- enzymes, monoamine oxidases (MAO), and flavin-containing monooxygenases (FMO). Targeted LC-MS/MS analysis of hepatocyte incubations using chemical inhibitors indicated that PQ was predominantly metabolized by CYPs 3A4, 1A2 and 2D6, MAO-A, -B and FMO-3. Confirmation of these results was sought by incubation of PQ with the corresponding recombinant enzymes. Small amounts of carboxyprimaquine (CPQ), the major observed PQ metabolite in vivo, were detected in recombinant MAO-A incubations along with another peak at m/z 261, and no significant formation of CPQ with any other recombinant enzymes was observed. Incubations with all recombinant enzymes identified as potentially active towards PQ from the hepatocyte-based assay resulted in significant parent loss over the course of 1 h. These results suggest that several enzymes, including CYPs in combination with FMOs and MAOs, play a role in the overall metabolism of PQ and indicate a major role for MAO-A. Future studies to elucidate the potential role in cytotoxicity and/or efficacy of the PQ metabolite observed at m/z 261, as observed in MAO-A isoenzyme studies, are needed.

Cognitive change and neuroimaging following immunoablative therapy and hematopoietic stem cell transplantation in multiple sclerosis: A pilot study.

BACKGROUND: Individuals with MS undergoing immunoablative therapy and hematopoietic stem cell transplantation (HSCT) show substantial decrease in brain volume over 2.4 months, presumably from chemotoxic effects, although other mechanisms have also been postulated. OBJECTIVE: We examined whether volume loss was accompanied by a concomitant decrease in cognition. White and gray matter volumes, and the effect of stem cell dosage were considered. METHODS: Seven individuals with rapidly progressing MS and poor prognosis underwent high dose immunosuppression and autologous HSCT. Neuropsychological testing and MRI scans were performed at baseline, 2 and 24 months post-procedure. RESULTS: Cognitive impairment was noted at all times in most participants. Median decline of 1.39% in total brain volume was noted 2 months post-HSCT. By 24 months a further decline of 1.65% was noted. At 2 months significant decline was observed for areas of executive functioning. At 24 months almost no significant declines were noted. No significant correlations were found between cognitive decline and change in imaging variables or stem cell dosage. CONCLUSIONS: Cognition changed in the early period following treatment but with little apparent relationship to volume changes. With temporal distance from the HSCT procedure, cognition returned to baseline levels. With the caution of a very small sample, preliminary results suggest that immunoablation and HSCT may have no lasting deleterious effects on cognition.

Detecting cognitive fatigue in multiple sclerosis: method matters.

BACKGROUND: Fatigue is a frequently reported and debilitating symptom in multiple sclerosis (MS). Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The effectiveness of the Paced Auditory Serial Addition Task (PASAT) and the Computerized Test of Information Processing (CTIP) at detecting CF was examined, as was the impact of methodology. Subjective fatigue was measured using the Fatigue Impact Scale (FIS). The relationship between objective and subjective fatigue was examined. METHODS: 70 MS and 72 healthy controls (HC) completed the PASAT (3″ and 2″), CTIP, and FIS as part of a larger battery. RESULTS: The MS and HCs performed worse on cognitively demanding tasks. Depending on methodology, PASAT performance varied between groups at the 3″ inter-stimulus interval (ISI) and the MS group showed greater susceptibility to CF as their ability to meet task demands declined as the task progressed. CTIP performance for both groups varied differently over time depending on task. The relationship between subjective and objective measures of fatigue varied depending on methodology, with PASAT generally correlating well with the Cognitive Dimension of the FIS. CONCLUSIONS: The PASAT is a sensitive measure of CF in MS. Additional information is obtained with different scoring methods, with percent dyad scoring method being most sensitive to CF. The ability to detect a relationship between objective and subjective measures varied with methodology.

Activation patterns in multiple sclerosis on the Computerized Tests of Information Processing.

RATIONALE: Multiple sclerosis (MS) patients exhibit cognitive deficits that negatively impact quality of life. The Relative Consequence Model suggests that problems with information processing speed (IPS) may be the basis for many of these cognitive difficulties. OBJECTIVE: To investigate, with functional magnetic resonance imaging (fMRI), if an IPS task (the Computerized Test of Information Processing (CTIP)) would reveal neurophysiological differences between MS patients and matched controls. METHODS: Performance and neural activation were investigated in twelve cognitively impaired MS patients and 12 matched controls as each performed the CTIP. The CTIP measures reaction time (RT) and errors on three tasks (simple RT, choice RT and semantic search RT) with increasing cognitive demands. RESULTS: Participants demonstrated increased RT with increased task complexity. Patients showed longer RTs for the choice RT condition than controls but the pattern of performance across tasks did not vary between groups. Errors were not significantly different between groups. Imaging results for both the choice and the semantic search conditions revealed significant differences between groups involving a compensatory increase in activation in MS participants compared to controls in prefrontal cortex and right temporal gyri. However, there were also areas of decreased activity in MS participants when compared with controls in left temporal gyri. CONCLUSIONS: Significantly different neural activation patterns between MS patients and controls were associated with IPS, as measured by the CTIP.

Meaningful change in cognition in multiple sclerosis: method matters.

OBJECTIVE: To determine if different methods of evaluating cognitive change over time yield measurably different outcomes. METHODS: Twelve cognitively impaired patients with clinically definite Multiple sclerosis (10 relapsing-remitting, 2 secondary progressive) underwent neuropsychological testing (baseline, 6, 12 months). Data was analysed using: t-tests evaluating group differences on individual tests, group differences in composite scores, reliable change analyses at the level of the individual, and comparisons regarding number of tests failed at each time point. RESULTS: Group t-tests on individual tests yielded no change. When tests were grouped according to theoretical constructs, analyses revealed change in processing speed. Reliable change estimates revealed that 16% of the sample deteriorated. When change was measured with respect to the number of domains affected at each time point, 58% of the sample deteriorated on at least one subtest. CONCLUSIONS: Methodology has a significant impact on interpretation of longitudinal data. In the same group of subjects, traditional group analyses documented no change in individual test scores or change on a single composite score. Analyses of individual results documented change from 16 to 58% of the sample. Advantages and disadvantages of each method were discussed. Findings have implications for interpretation of longitudinal studies.

Do estuaries pose a toxic contamination risk for wading birds?

The impact of potentially toxic chemicals on wildlife is commonly assessed by comparing the intake of the contaminant with the "no observable effects level" (NOAEL) of intake. It is known, however, that there are considerable uncertainties inherent in this method. This study presents a Monte-Carlo based model to assess the degree of risk posed to birds (dunlin, Calidris alpina) from important estuarine habitats, and to show the limitations of such risk assessments, particularly with regard to data availability. The model was applied to predict the uptake of metals (Hg, Pb) in this shorebird species in Poole Harbour and the Severn Estuary/Bristol Channel, UK, two internationally important shorebird habitats. The results show that in both areas, Pb and Hg concentrations may pose an ecologically relevant toxic risk to wading birds. For Pb, uncertainty in NOAEL values dominates the overall uncertainty. Use of lethal toxicity data (LD50/100) was investigated as a method for assessing sub-lethal impacts from Hg. It was found that this method led to a significant under-estimate of the potential impact of Hg contamination, compared with direct estimation of NOAEL.

Genomic and genetic approaches for the identification of antifungal drug targets.

Understanding how novel antifungal compounds work in target cells is useful not only in facilitating the discovery of new drugs but also new tools that can be used for further exploration of the targeted biological pathways and their regulation. Various genomic and genetic technologies have been developed in the model yeast Saccharomyces cerevisiae, and have been successfully used to identify drug target pathways. This review discusses the methods developed for some of these technologies, and how they have been used to evaluate the cellular pathways affected by a variety of therapeutic drugs and inhibitors. The advantages and disadvantages of each method are considered, and new advances are highlighted where applicable. The investigation of the mechanism of action of new antifungal compounds will undoubtedly lead to the development of new antifungal therapies targeting new fungal pathways that are more specific and less toxic than currently available antifungal drugs.

Lead contamination and associated disease in captive and reintroduced red kites Milvus milvus in England.

Since 1989, a red kite Milvus milvus reintroduction programme has been underway in the United Kingdom, with 4-6 week old nestlings brought into captivity and held for 6-8 weeks before reintroduction. As scavengers, red kites may consume unretrieved game, and ingest shot or lead (Pb) fragments in their prey's flesh. We evaluated exposure to Pb in captive and wild red kites by taking blood samples from 125 captive young red kites prior to release, through analysing 264 pellets (regurgitated by wild birds) collected from under a roost site, and analysing Pb concentrations in livers and/or bones of 87 red kites found dead between 1995 and 2003. Lead isotope analyses of livers were also conducted in an effort to identify Pb exposure routes. Forty-six (36.8%) kites sampled prior to release had elevated blood Pb concentrations (201-3340 microg l(-1)). The source of this Pb was probably small fragments of lead ammunition in the carcasses of birds or mammals either fed to the nestlings by their parents or, more likely, subsequently whilst in captivity. Once released, kites were also exposed to lead shot in their food, and a minimum of 1.5-2.3% of regurgitated pellets contained Pb gunshot. Seven of 44 red kites found dead or that were captured sick and died within a few days had elevated (>6 mg kg(-1) dry weight [d.w.]) liver Pb concentrations, and six of these (14%) had concentrations of >15 mg kg(-1) d.w., compatible with fatal Pb poisoning. Post-mortem analyses indicated that two of these birds had died of other causes (poisoning by rodenticide and a banned agricultural pesticide); the remaining four (9%) probably died of Pb poisoning. Bone samples from 86 red kites showed a skewed distribution of Pb concentration, and 18 samples (21%) had Pb concentrations >20 mg kg(-1) d.w., indicating elevated exposure to Pb at some stage in the birds' life. Lead isotopic signatures (Pb (208/206); Pb (206/207)) in liver samples of the majority of kites were compatible with those found in lead shot extracted from regurgitated pellets. Lead isotope ratios found in the livers of kites with very low Pb concentrations were distinct from UK petrol Pb isotopic signatures, indicating that birds were exposed to little residual petrol Pb. We conclude that the primary source of Pb to which red kites are exposed is lead ammunition (shotgun pellets or rifle bullets), or fragments thereof, in their food sources; in some cases exposure appears sufficient to be fatal. We make recommendations to reduce Pb poisoning in both captive and wild red kites and other scavenging species.

Heavy metal contamination in bats in Britain.

Toxic metals are bioaccumulated by insectivorous mammals but few studies (none from Britain) have quantified residues in bats. We measured renal mercury (Hg), lead (Pb) and cadmium (Cd) concentrations in bats from south-west England to determine how they varied with species, sex, age, and over time, and if they were likely to cause adverse effects. Residues were generally highest in whiskered bats (Myotis mystacinus). Compared with other species, pipistrelle (Pipistrellus spp) and Natterer's bats (Myotis nattereri) had significantly lower kidney Hg and Pb concentrations, respectively. Renal Hg increased over time in pipistrelles but the contributory sources are unknown. Kidney Pb did not decrease over time despite concurrent declines in atmospheric Pb. Overall, median renal metal concentrations were similar to those in bats from mainland Europe and 6- to 10-fold below those associated with clinical effect, although 5% of pipistrelles had kidney Pb residues diagnostic of acute lead poisoning.

Biologically active quassinoids and their chemistry: potential leads for drug design.

Quassinoids are highly oxygenated triterpenes, which were isolated as bitter principles from the plants of Simaroubaceae family. Their synthesis has attracted much attention because of the wide spectrum of their biological properties. The most prevalent quassinoids have C-20 picrasane skeleton, some known as bruceolides as they were isolated from the genus Brucea, which showed marked antileukemic and antimalarial activities.

Synthesis of A/B-ring partial analogs of bruceantin as potential antimalarial agents.

Bruceantin (1), a classical quassinoid with the highest reported antimalarial activity among the quassinoids examined thus far, was selected as a natural product lead for the design of a series of A/B-ring analogs. A viable strategy for the synthesis of the series was developed. The functionalized A-ring and the C-15 ester moiety in bruceantin are incorporated in all designed compounds. The preliminary bioassay results will be discussed in detail.