Four Undescribed Stilbenoid Derivatives from the Aerial Parts of Dendrobium officinale with their α-Glucosidase and α-Amylase Inhibitory Activity.

In this study, four undescribed bibenzyl derivatives (1-4), together with seven known compounds (5-11) were isolated from the aerial parts of Dendrobium officinale. Their chemical structures were determined to be (7'S,8'S) -9''-acetyldendrocandin U (1), (7'S,8'S) -4'-methoxydendrocandin T (2), (7'R,8'S) -dendrocandin B (3), (1S,2R) -5'''-methoxydendrofindlaphenol C (4) by analyzing of the spectroscopic data including HR-ESI-MS, 1D-, and 2D-NMR spectra. The absolute configurations of compounds 1-4 were determined by the electronic circular dichroism (ECD) spectra. Compounds 1-3, 5, 10 and 11 inhibited α-glucosidase with the IC50 values ranging from 56.3 to 165.3 µM, compounds 1-3, 5, 7-10 inhibited α-amylase with the IC50 values ranging from 65.2 to 177.6 µM.

Latent and active tuberculosis development in patients with rheumatoid arthritis receiving biologic disease-modifying antirheumatic drugs: A single-center prospective study.

Biologics have revolutionized the treatment of rheumatoid arthritis (RA) in recent years. However, data from clinical trials and actual clinical practice have shown that biologics currently in use may constitute a risk factor for reactivation of tuberculosis (TB) in patients with latent TB infection. Therefore, screening for latent and active TB infection is mandatory before initiating biologic therapy in patients with RA. This prospective study aimed to analyze the clinical characteristics of patients with RA receiving biologic disease-modifying antirheumatic drugs at Bach Mai Hospital, Vietnam, between 2017 and 2022, and to identify factors affecting the occurrence of active and latent TB infection among these patients. Over a 12-month follow-up period, latent TB infection was confirmed in 20% of the total 180 included patients, while 3 (1.7%) patients developed active TB (one case of pulmonary, pleural, and gluteal TB each). History of TB risk factor exposure and lack of education were significantly associated with the occurrence of active and latent TB infection, with odds ratios (95% confidence intervals [CIs]) of 1.98 (1.78; 2.2) and 1.45 (1.31; 1.6), respectively. Follow-up duration and number of X-ray, computed tomography, bronchoscopy, and sputum acid-fast bacteria examinations were identified as factors that can aid in the early diagnosis of latent TB, with odds ratios (95% CIs) of 1.00 (1; 1.01), 1.02 (1; 1.05), 1.12 (1.11; 1.2), 1.11 (1.09; 1.2), and 1.13 (1.09; 1.17), respectively. Our study showed that, in countries with high TB burden like Vietnam, latent TB infection has high prevalence among patients with RA. We also provide useful information for the screening, monitoring, and treatment of latent and active TB infection in patients with RA.

A Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase Tuberculosis Clinical Trials.

Rationale: We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary tuberculosis (TB). Objectives: We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcomes for all participants were achieved. Methods: A PPTR event was defined as the occurrence of one or more prespecified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. Measurements and Main Results: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 wk). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome and between 13.8% and 14.7% of participants with favorable and not-assessable outcomes. A total of 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve a disease-free cure. Conclusions: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials.

Pharmacy students' preparation to provide pharmaceutical care for patients with non-communicable diseases in six ASEAN countries: A qualitative study.

INTRODUCTION: Pharmacy education programs prepare graduates to promote health for patients with noncommunicable disease (NCDs), but there is limited information concerning Association of South East Asia Nations (ASEAN) countries. The study aim was to synthesize academic staff's, alumni's, and alumni supervisors' perspectives on preparation for students to provide pharmaceutical care in NCDs. METHODS: A qualitative research design was used. In-depth interviews with structured questions following the Context, Input, Process, and Product/Outcomes model framework were conducted with four academic staff, three alumni, and three alumni supervisors from six study sites in six countries. Interview questions were constructed in Thai and translated to English by using forward and backward translation. Verbatim transcriptions were used to perform thematic analysis with investigator triangulation. RESULTS: Sixty participants were included. The context showed three main themes related to Burden of NCDs, Pharmacist Roles in NCDs, and Goals. The input showed three main themes of Teaching Methods, Development Plans for Academic Staff, and Budgets and Infrastructure. The process showed one main theme of Struggles in Teaching Methods. The outcomes/outputs showed three main themes of Individual, Organizational, and Professional Levels. Schools need curricula that focus on NCDs, pharmacist competency and skills, and academic preparation of students for practice. Gaps limiting achievement of goals included lack of well-trained academic staff, limited learning facilities, self-learning opportunities, acceptance from other health professionals, and career ladders. CONCLUSIONS: The preparation of pharmacy students varied in six ASEAN countries. Pharmacy education programs must address existing gaps that limit achievement of goals related to NCDs.

A logistic regression model based on inpatient health records to predict drug-induced liver injury caused by ramipril-An angiotensin-converting enzyme inhibitor.

Drug-induced liver injury (DILI) is a rare side effect of angiotensin-converting enzyme inhibitors (ACEIs). Ramipril is a widely used ACE compound because of its effectiveness in the treatment of hypertension and heart failure, as well as its low risk of adverse effects. However, the clinical features of ramipril, and the risk of DILI, have not been adequately studied. A retrospective cohort study was performed based on data from 3909 inpatients to compare the risk of DILI conferred by ramipril and other ACEIs. A logistic regression model was then constructed and validated against data from 1686 patients using ramipril, of which 117 patients were diagnosed with DILI. The use of ramipril increased the risk of DILI by 2.68 times (odds ratio = 2.68; 95% confident interval (CI):1.96-3.71) compared with the group using other ACEIs. The clinical features of DILI in the ramipril group were similar to those from the ACEI group (P>0.05), except that the ALT level was higher (P<0.05). A logistic regression model including Body mass index (BMI), comorbidity, liver disease, daily dose, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) was built and successfully validated for DILI risk prediction, with the area under the receiver operating characteristic curve of the model of 0.82 (95% CI: 0.752-0.888). We recommend that clinicians should be aware of the levels of ALT and ALP as well as BMI, comorbidities, and liver disease before prescribing ramipril to avoid the risk of DILI in patients.

Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout.

Allopurinol (ALP) is commonly used as a drug for gout treatment. However, ALP is known to cause cutaneous adverse reactions (CARs) in patients. The HLA-B*58:01 allele is considered a biomarker of severe CAR (SCAR) in patients with gout, with symptoms of Stevens Johnson syndrome, and with toxic epidermal necrolysis. However, in patients with gout and mild cutaneous adverse drug reactions (MCARs), the role of HLA-allele polymorphisms has not been thoroughly investigated. In this study, 50 samples from ALP-tolerant patients and ALP-induced MCARs patients were genotyped in order to examine the polymorphisms of their HLA-A and HLA-B alleles. Our results showed that the frequencies of HLA-A*02:01/HLA-A*24:02 and HLA-A*02:01/HLA-A*29:01, the dual haplotypes in HLA-A, in patients with ALP-induced MCARs were relatively high, at 33.3% (7/21), which was HLA-B*58:01-independent, while the frequency of these dual haplotypes in the HLA-A locus in ALP-tolerant patients was only 3.45% (1/29). The HLA-B*58:01 allele was detected in 38% (8/21) of patients with ALP-induced MCARs, and in 3.45% (1/29) of ALP-tolerant patients. Notably, although HLA-B*58:01 may be a cause for the occurrence of MCARs in patients with gout, this correlation was not as strong as that previously reported in patients with SCAR. In conclusion, in addition to the HLA-B*58:01 allele, the presence of the dual haplotypes of HLA-A*02:01/HLA-A*24:02 and/or HLA-A*02:01/HLA-A*29:01 in the HLA-A locus may also play an important role in the appearance of ALP-induced MCARs in the Vietnamese population. The obtained primary data may contribute to the development of suitable treatments for patients with gout not only in Vietnam but also in other Asian countries.

Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region.

BACKGROUND: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region. METHODS: RA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission. FINDINGS: A total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission. INTERPRETATION: Remission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.

Viral Metagenomic Analysis of Cerebrospinal Fluid from Patients with Acute Central Nervous System Infections of Unknown Origin, Vietnam.

Central nervous system (CNS) infection is a serious neurologic condition, although the etiology remains unknown in >50% of patients. We used metagenomic next-generation sequencing to detect viruses in 204 cerebrospinal fluid (CSF) samples from patients with acute CNS infection who were enrolled from Vietnam hospitals during 2012-2016. We detected 8 viral species in 107/204 (52.4%) of CSF samples. After virus-specific PCR confirmation, the detection rate was lowered to 30/204 (14.7%). Enteroviruses were the most common viruses detected (n = 23), followed by hepatitis B virus (3), HIV (2), molluscum contagiosum virus (1), and gemycircularvirus (1). Analysis of enterovirus sequences revealed the predominance of echovirus 30 (9). Phylogenetically, the echovirus 30 strains belonged to genogroup V and VIIb. Our results expanded knowledge about the clinical burden of enterovirus in Vietnam and underscore the challenges of identifying a plausible viral pathogen in CSF of patients with CNS infections.

Chemical constituents and biological activities of the fruits of Knema pachycarpa de Wilde.

The n-hexane extract of Knema pachycarpa fruits (Myristicaceae family), exhibiting strong anti-acetylcholinesterase activity, was investigated by gas chromatography/mass spectrometry and then purified by column chromatography. Guided by GC/MS profiling and bioassay, chromatographic separations led to the isolation of five new compounds: two anacardic acid derivatives 1-2, two cardanol derivatives 3-4 and a cardol derivative 5, along with mixtures of known phenolic lipids 6-9. The chemical structures were determined by various spectroscopic methods. New isolated compounds 1-5 were evaluated for their cytotoxicity and anti-acetylcholinesterase activity. Cardanol 3 and cardol 5 were the most active compounds in the acetylcholinesterase inhibitory assay with IC50 values of 2.60 ± 0.24 µM and 2.46 ± 0.23 µM, respectively. Cardanol 4 and cardol 5 showed moderate cytotoxicity against Hela and MCF-7 cancer cell lines with IC50 values ranging from 31.36 ± 0.41 µM to 41.30 ± 2.49 µM.

The impact of sexual harassment on obesity in female adolescents: An update and perspective to control.

BACKGROUND AND AIMS: Sexual victimization, happened during childhood and beyond, is known to be a substantial contributing factor for obesity development later in life. This work aims to bring about updated information on the relationship between sexual harassment and obesity. METHODS: Based on an intensive scientific literature review in Google Scholar, Pubmed databases, the total of 106 studies (N = 141,199) were assessed including 52 studies on the connection between negative lifetime impacts and obesity, 11 studies on post-traumatic stress disorder (PTSD) symptoms with proposed biological mechanisms related to obesity, 15 studies on the relationship between major depressive disorder (MDD) symptoms and obesity, 11 studies on the body dismorphic disorder (BDD) and 17 studies on the binge eating disorder (BED) were also examined to evaluate the association of obesity and traumatic life experiences. RESULTS: Although 40-70% of all cases related to obesity have been considered to be hereditary, many experts argue that deviations in the environment contribute to excessive food intake and depressed physical activity in numerous Western countries. Several studies have identified that childhood sexual abuse (CSA) may be nearly as common as obesity. However, just a few researchers have taken notice of the possible connection between these two. CONCLUSIONS: By mentioning some possible obesity-related psychological disorders in response to CSA, we present updated information on the relationship between sexual harassment and obesity.

Biodegradation of propanil by Acinetobacter baumannii DT in a biofilm-batch reactor and effects of butachlor on the degradation process.

The herbicide, propanil, has been extensively applied in weed control, which causes serious environmental pollution. Acinetobacter baumannii DT isolated from soil has been used to determine the degradation rates of propanil and 3,4-dichloroaniline by freely suspended and biofilm cells. The results showed that the bacterial isolate could utilize both compounds as sole carbon and nitrogen sources. Edwards's model could be fitted well to the degradation kinetics of propanil, with the maximum degradation of 0.027 ± 0.003 mM h-1. The investigation of the degradation pathway showed that A. baumannii DT transformed propanil to 3,4-dichloroaniline before being completely degraded via the ortho-cleavage pathway. In addition, A. baumannii DT showed high tolerance to butachlor, a herbicide usually mixed with propanil to enhance weed control. The presence of propanil and butachlor in the liquid media increased the cell surface hydrophobicity and biofilm formation. Moreover, the biofilm reactor showed increased degradation rates of propanil and butachlor and high tolerance of bacteria to these chemicals. The obtained results showed that A. baumannii DT has a high potential in the degradation of propanil.

Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam.

Drug-resistant tuberculosis (TB) is a serious global problem, and pathogen factors involved in the transmission of isoniazid (INH)-resistant TB have not been fully investigated. We performed whole genome sequencing of 332 clinical Mycobacterium tuberculosis (Mtb) isolates collected from patients newly diagnosed with smear-positive pulmonary TB in Hanoi, Vietnam. Using a bacterial genome-wide approach based on linear mixed models, we investigated the associations between 31-bp k-mers and clustered strains harboring katG-S315T, a major INH-resistance mutation in the present cohort and in the second panel previously published in South Africa. Five statistically significant genes, namely, PPE18/19, gid, emrB, Rv1588c, and pncA, were shared by the two panels. We further identified variants of the genes responsible for these k-mers, which are relevant to the spread of INH-resistant strains. Phylogenetic convergence test showed that variants relevant to PPE46/47-like chimeric genes were significantly associated with the same phenotype in Hanoi. The associations were further confirmed after adjustment for the confounders. These findings suggest that genomic variations of the pathogen facilitate the expansion of INH-resistance TB, at least in part, and our study provides a new insight into the mechanisms by which drug-resistant Mtb maintains fitness and spreads in Asia and Africa.

Does Ralstonia eutropha, rich in poly-ß hydroxybutyrate (PHB), protect blue mussel larvae against pathogenic vibrios?

The natural amorphous polymer poly-ß-hydroxybutyrate (PHB-A: lyophilized Ralstonia eutropha containing 75% PHB) was used as a biological agent to control bacterial pathogens of blue mussel (Mytilus edulis) larvae. The larvae were supplied with PHB-A at a concentration of 1 or 10 mg/L for 6 or 24 hr, followed by exposure to either the rifampicin-resistant pathogen Vibrio splendidus or Vibrio coralliilyticus at a concentration of 105 CFU/ml. Larvae pretreated 6 hr with PHB-A (1 mg/L) survived a Vibrio challenge better relative to 24 hr pretreatment. After 96 hr of pathogen exposure, the survival of PHB-A-treated mussel larvae was 1.41- and 1.76-fold higher than the non-treated larvae when challenged with V. splendidus and V. coralliilyticus, respectively. Growth inhibition of the two pathogens at four concentrations of the monomer ß-HB (1, 5, 25 and 125 mM) was tested in vitro in LB35 medium, buffered at two different pH values (pH 7 and pH 8). The highest concentration of 125 mM significantly inhibited the pathogen growth in comparison to the lower levels. The effect of ß-HB on the production of virulence factors in the tested pathogenic Vibrios revealed a variable pattern of responses.

Ralstonia eutropha, containing high poly-ß-hydroxybutyrate levels, regulates the immune response in mussel larvae challenged with Vibrio coralliilyticus.

Marine invertebrates rely mainly on innate immune mechanisms that include both humoral and cellular responses. Antimicrobial peptides (AMPs), lysozyme and phenoloxidase activity, are important components of the innate immune defense system in marine invertebrates. They provide an immediate and rapid response to invading microorganisms. The impact of amorphous poly-ß-hydroxybutyrate (PHB-A) (1 mg PHB-A L-1) on gene expression of the AMPs mytimycin, mytilinB, defensin and the hydrolytic enzyme lysozyme in infected blue mussel larvae was investigated during "in vivo" challenge tests with Vibrio coralliilyticus (105 CFU mL-1). RNAs were isolated from mussel larvae tissue, and AMPs were quantified by q-PCR using the 18srRNA gene as a housekeeping gene. Our data demonstrated that AMPs genes had a tendency to be upregulated in challenged mussel larvae, and the strongest expression was observed from 24 h post-exposure onwards. The presence of both PHB-A and the pathogen stimulated the APMs gene expression, however no significant differences were noticed between treatments or between exposure time to the pathogen V. coralliilyticus. Looking at the phenoloxidase activity in the infected mussels, it was observed that the addition of PHB-A significantly increased the activity.

Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam.

BACKGROUND: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. METHODS: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references.    Results: Overall, viral pathogens were detected in a total count of 270/294 (91.8%, 95% CI 88.1-94.7) by the Luminex among reference assays, whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. CONCLUSIONS: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.

Estimating the Internal Dose for 131I Production Workers From Air Sampling Method.

Besides the most common methods of internal dose assessment from inhaled 131I, that are thyroid monitoring and urine analysis, air sampling is a possible way but rarely used for dose estimate. This study aimed to focus on the utilisation of portable air sampler to estimate the internal dose for workers working at 131I production facility. In addition, internal dose estimated from urine analysis at the same time was carried out for comparison. Based on this research, it was found that air monitoring can be done efficiently as urine monitoring if the following conditions are met: (1) the indoor areas are not large, (2) sampling sites need to be placed as near breathing zone as possible and (3) the time-micro-environment patterns of monitored workers are collected carefully.

Infection control and tuberculosis among health care workers in Viet Nam, 2009-2013: a cross-sectional survey.

BACKGROUND: Data on tuberculosis (TB) among health care workers (HCW) and TB infection control (TBIC) indicators are rarely available at national level. We assessed multi-year trends in notification data of TB among HCW and explored possible associations with TBIC indicators. METHODS: Notified TB incidence among HCW and 3 other TBIC indicators were collected annually from all 64 provincial and 3 national TB facilities in Vietnam. Time trends in TB notification between 2009 and 2013 were assessed using linear regression analysis. Multivariate regression models were applied to assess associations between the facility-specific 5-year notification rate and TBIC indicators. RESULTS: Forty-seven (70 %) of 67 facilities contributed data annually over five years; 15 reported at least one HCW with TB in 2009 compared to six in 2013. The TB notification rate dropped from 593 to 197 per 100,000 HCW (ptrend = 0.02). Among 104 TB cases reported, 30 were employed at TB wards, 24 at other clinical wards, ten in the microbiology laboratory, six at the MDR-TB ward, and 34 in other positions. The proportion of facilities with a TBIC plan and focal person remained relatively stable between 70 % and 84 %. The proportion of facilities providing personal protective equipment (PPE) to their staff increased over time. Facilities with a TBIC focal person were 7.6 times more likely to report any TB cases than facilities without a focal person. CONCLUSIONS: The TB notification rates among HCW seemed to decrease over time. Availability of PPE increased over the same period. Appointing a TBIC focal person was associated with reporting of TB cases among HCW. It remains unclear whether TBIC measures helped in reduction of the TB notification rates in HCW.

Using smartphone as a motion detector to collect time-microenvironment data for estimating the inhalation dose.

During the production of iodine-131 from neutron irradiated tellurium dioxide by the dry distillation, a considerable amount of (131)I vapor is dispersed to the indoor air. People who routinely work at the production area may result in a significant risk of exposure to chronic intake by inhaled (131)I. This study aims to estimate the inhalation dose for individuals manipulating the (131)I at a radioisotope production. By using an application installed on smartphones, we collected the time-microenvironment data spent by a radiation group during work days in 2015. Simultaneously, we used a portable air sampler combined with radioiodine cartridges for grabbing the indoor air samples and then the daily averaged (131)I concentration was calculated. Finally, the time-microenvironment data jointed with the concentration to estimate the inhalation dose for the workers. The result showed that most of the workers had the annual internal dose in 1÷6mSv. We concluded that using smartphone as a motion detector is a possible and reliable way instead of the questionnaires, diary or GPS-based method. It is, however, only suitable for monitoring on fixed indoor environments and limited the targeted people.

Litsea Species as Potential Antiviral Plant Sources.

Litsea verticillata Hance (Lauraceae), a Chinese medicine used to treat swelling caused by injury or by snake bites, was the first plant identified by our National Institutes of Health (NIH)-funded International Cooperative Biodiversity Group (ICBG) project to exhibit anti-HIV activities. From this plant, we discovered a class of 8 novel litseane compounds, prototypic sesquiterpenes, all of which demonstrated anti-HIV activities. In subsequent studies, 26 additional compounds of different structural types were identified. During our continuing investigation of this plant species, we identified two new litseanes, litseaverticillols L and M, and a new sesquiterpene butenolide, litseasesquibutenolide. Litseaverticillols L and M were found to inhibit HIV-1 replication, with an IC[Formula: see text] value of 49.6[Formula: see text][Formula: see text]M. To further determine the antiviral properties of this plant, several relatively abundant isolates, including a litseane compound, two eudesmane sesquiterpenes and three lignans, were evaluated against an additional 21 viral targets. Lignans 8 and 9 were shown to be active against the Epstein-Barr Virus (EBV), with EC[Formula: see text] values of 22.0[Formula: see text][Formula: see text]M ([Formula: see text]) and 16.2[Formula: see text][Formula: see text]M ([Formula: see text]), respectively. Since many antiviral compounds have been discovered in L. verticillata, we further prepared 38 plant extracts made from the different plant parts of 9 additional Litsea species. These extracts were evaluated for their anti-HIV and cytotoxic activities, and four of the extracts, which ranged across three different species, displayed 97-100% inhibitory effects against HIV replication without showing cytotoxicity to a panel of human cell lines at a concentration of 20 µg/mL.

Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia.

Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV . Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37 RV . Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 µm in MABA assay, respectively, and 91.7 and 168.3 µm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 µm in MABA assay and 100.2 µm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives.