In silico screening of Fyn kinase inhibitors using classification-based QSAR model, molecular docking, molecular dynamics and ADME study.

This study aimed to use a computational approach that combined the classification-based QSAR model, molecular docking, ADME studies, and molecular dynamics (MD) to identify potential inhibitors of Fyn kinase. First, a robust classification model was developed from a dataset of 1,078 compounds with known Fyn kinase inhibitory activity, using the XGBoost algorithm. After that, molecular docking was performed between potential compounds identified from the QSAR model and Fyn kinase to assess their binding strengths and key interactions, followed by MD simulations. ADME studies were additionally conducted to preliminarily evaluate the pharmacokinetics and drug-like characteristics of these compounds. The results showed that our obtained model exhibited good predictive performance with an accuracy of 0.95 on the test set, affirming its reliability in identifying potent Fyn kinase inhibitors. Through the application of this model in conjunction with molecular docking and ADME studies, nine compounds were identified as potential Fyn kinase inhibitors, including 208 (ZINC70708110), 728 (ZINC8792432), 734 (ZINC8792187), 736 (ZINC8792350), 738 (ZINC8792286), 739 (ZINC8792309), 817 (ZINC33901069), 852 (ZINC20759145), and 1227 (ZINC100006936). MD simulations further demonstrated that the four most promising compounds, 728, 734, 736, and 852 exhibited stable binding with Fyn kinase during the simulation process. Additionally, a web-based platform ( https://fynkinase.streamlit.app/ ) has been developed to streamline the screening process. This platform enables users to predict the activity of their substances of interest on Fyn kinase from their SMILES, using our classification-based QSAR model and molecular docking.

Chemical Profile and Antioxidant Capacity of Propolis from Tetragonula, Lepidotrigona, Lisotrigona and Homotrigona Stingless Bee Species in Vietnam.

The present study aimed to analyze and compare the chemical profile and antioxidant capacity of propolis from different bee species and different regions. The chemical profiles of propolis from six stingless bee species (Tetragonula iridipennis, T. laeviceps, Lepidotrigona terminata, L. ventralis, Lisotrigona carpenteri and Homotrigona apicalis) collected from a total of eight locations in Vietnam were investigated by gas chromatography-mass spectrometry (GC-MS). More than 70 compounds were identified, amongst which phenolic lipids (cardanols, resorcinols and anacardic acids), aromatic acids, triterpenes and xanthones. Taxonomic markers for Mangifera indica (phenolic lipids and cycloartane triterpenes) were detected in propolis from bees of the genera Tetragonula and Lepidotrigona, although in different amounts, whereas propolis from H. apicalis was characterized by triterpenes of the amyrine type, typical of dipterocarp trees. A clear discrimination between both groups was observed by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). Propolis from Tetragonula and Lepidotrigona spp. and from Lisotrigona carpenteri, which is rich in xanthones, possesses higher radical scavenging and ferric-reducing capacity than that from H. apicalis. Propolis produced by all six stingless bee species in Vietnam was analyzed for the first time. In addition, this is the first report on L. carpenteri propolis.

Characterization of Antioxidant and α-Glucosidase Inhibitory Compounds of Cratoxylum formosum ssp. pruniflorum and Optimization of Extraction Condition.

Cratoxylum formosum ssp. pruniflorum (Kurz.) Gogel (Guttiferae), called kuding tea, is widely distributed in Southeast Asia. In this study, the constituents and biological activity of C. formosum ssp. pruniflorum were investigated. Extract of its leaves, roots and stems showed antioxidant and α-glucosidase inhibitory activity. Interestingly, comparison of the metabolite profiles of leaves, roots and stems of C. formosum ssp. pruniflorum by LC-MS analysis showed a great difference between the roots and leaves, whereas the roots and stems were quite similar. Purification of the roots and leaves of C. formosum ssp. pruniflorum through various chromatographic techniques resulted in the isolation of 25 compounds. The structures of isolated compounds were elucidated on the basis of spectroscopic analysis as 18 xanthones, 5 flavonoids, a benzophenone and a phenolic compound. Among them, a xanthone (16) and a benzophenone (19) were first reported from nature. Evaluation of biological activity revealed that xanthones had a potent α-glucosidase inhibitory activity, while flavonoids were responsible for the antioxidant activity. To maximize the biological activity, yield and total phenolic content of C. formosum ssp. pruniflorum, extraction conditions such as extraction solvent, time and temperature were optimized using response surface methodology with Box-Behnken Design (BBD). Regression analysis showed a good fit of the experimental data, and the optimal condition was obtained as MeOH concentration in EtOAc, 88.1%; extraction time, 6.02 h; and extraction temperature 60.0 °C. α-Glucosidase inhibitory activity, yield and total phenolic content under the optimal condition were found to be 72.2% inhibition, 10.3% and 163.9 mg GAE/g extract, respectively. These results provide useful information about C. formosum ssp. pruniflorum as functional foods for oxidative stress-related metabolic diseases.

Antimicrobial, Cytotoxic, and α-Glucosidase Inhibitory Activities of Ethanol Extract and Chemical Constituents Isolated from Homotrigona apicalis Propolis-In Vitro and Molecular Docking Studies.

The chemical investigation of Homotrigona apicalis propolis collected in Binh Dinh province, Vietnam, led to the isolation of nine compounds, including four sesquiterpenes: spathulenol (1), 1αH,5ßH-aromandendrane-4ß,10α-diol (2), 1ß,6α-dihydroxy-4(15)-eudesmene (3), and 1ßH,5ßH-aromandendrane-4α,10ß-diol (4); three triterpenes: acetyl oleanolic acid (5), 3α-hydroxytirucalla-8,24-dien-21-oic acid (6), and ursolic acid (7); and two xanthones: cochinchinone A (8) and α-mangostin (9). Sesquiterpens 1-4 and triterpene 6 were isolated for the first time from stingless bee propolis. Plants in the Cratoxylum and Aglaia genus were suggested as resin sources of the propolis sample. In the antibacterial activity evaluation, the EtOH extract only showed moderate activity on S. aureus, while the isolated compounds 7-9 showed good antibacterial activity, with IC50 values of 0.56 to 17.33 µg/mL. The EtOH extract displayed selective cytotoxicity against the A-549 cancer cell line, with IC50 values of 22.82 ± 0.86 µg/mL, and the xanthones 8 and 9 exhibited good activity against the KB, HepG-2, and A-549 cancer cell lines, with IC50 values ranging from 7.55 ± 0.25 µg/mL to 29.27 ± 2.07 µg/mL. The cytotoxic effects of xanthones 8 and 9 were determined by the inhibition of the EGFR and HER2 pathways using a molecular docking study. Compounds 8 and 9 displayed strong binding affinity with EFGR and HER2, with values of -9.3 to -9.9 kcal/mol. Compounds 5, 8, and 9 showed potential α-glucosidase inhibitory activities, which were further confirmed by computational studies. The binding energies of compounds 5, 8, and 9 were lower than that of arcabose.

Mangifera indica as propolis source: what exactly do bees collect?

OBJECTIVE: The mango tree Mangifera indica is known as one of the botanical sources of propolis in Tropical regions. There are two different materials which bees can collect from a mango tree to produce propolis: the resin of the tree bark, and the latex found on the fruits. We performed the study of the chemical profile of mango resin in comparison with propolis in order to clarify its importance as propolis source. RESULTS: We compared the chemical profiles (by GC-MS analysis of ethanol extracts after silylation) of the resin and samples of propolis: of stingless bees (3 Vietnames, 2 Indonesian), and one of Apis mellifera from Thailand. In the resin and all propolis samples, 25 compounds were identified: fatty acids, cardanols (alk(en)yl phenols), cardols, anacardic acids, triterpene alcohols and ketones, cycloartane type triterpenic acids. All samples have the same qualitative composition but there are important quantitative differences. Considering literature data on mango latex, we conclude that bees of different species, make use of the two propolis sources offered by mango: bark resin and fruit latex, in different proportions. We also confirmed for the first time the presence of alk(en)yl phenols and anacardic acids in the tree bark resin of mango.

Phytochemical analysis of Vietnamese propolis produced by the stingless bee Lisotrigona cacciae.

Propolis produced by the stingless bee Lisotrigona cacciae was studied for the first time. Using different chromatographic procedures, a total of eighteen constituents (phenols and triterpenes) were isolated, among which flavane 1, homoisoflavanes 2-4, and xanthones 5 and 6 were new for propolis. Propolis extract was also characterized by gas chromatography/mass spectrometry and other fifteen constituents were identified. The xanthone α-mangostin (8) demonstrated significant activity against Staphylococcus aureus with MIC and MBC 0.31 µg/ml, followed by 7,4'-dihydroxy-5-methoxy-8-methylflavane (1) with MIC 78 µg/ml and MBC 156 µg/ml. 10,11- Dihydroxydracaenone C (4), a component bearing ortho-hydroxyl groups, was the only compound displaying radical scavenging ability. Triple botanical origin of the sample was defined, consisting of Dracaena cochinchinensis, Cratoxylum cochinchinense and Mangifera indica. D. cochinchinensis is a new resin source of propolis.

Correction: Suprafenacine, an Indazole-Hydrazide Agent, Targets Cancer Cells Through Microtubule Destabilization.

[This corrects the article DOI: 10.1371/journal.pone.0110955.].

Epidemiological, Serological, and Virological Features of Dengue in Nha Trang City, Vietnam.

Vietnam is endemic for dengue. We conducted a series of retrospective and prospective studies to characterize the epidemiology of dengue and population mobility patterns in Nha Trang city, Vietnam, with a view to rational design of trials of community-level interventions. A 10-year time series of dengue case notifications showed pronounced interannual variability, as well as spatial heterogeneity in ward-level dengue incidence (median annual coefficient of variation k = 0.47). Of 451 children aged 1-10 years enrolled in a cross-sectional serosurvey, almost one-third had evidence of a past dengue virus (DENV) infection, with older children more likely to have a multitypic response indicative of past exposure to ≥ 1 serotype. All four DENV serotypes were detected in hospitalized patients during 8 months of sampling in 2015. Mobility data collected from 1,000 children and young adults via prospective travel diaries showed that, although all ages spent approximately half of their daytime hours (5:00 am-9:00 pm) at home, younger age groups (≤ 14 years) spent a significantly greater proportion of their time within 500 m of home than older respondents. Together these findings inform the rational design of future trials of dengue preventive interventions in this setting by identifying 1) children < 7 years as an optimal target group for a flavivirus-naive serological cohort, 2) children and young adults as the predominant patient population for a study with a clinical end point of symptomatic dengue, and 3) substantial spatial and temporal variations in DENV transmission, with a consequent requirement for a trial to be large enough and of long enough duration to overcome this heterogeneity.

Xanthine oxidase inhibitors from Archidendron clypearia (Jack.) I.C. Nielsen: Results from systematic screening of Vietnamese medicinal plants.

OBJECTIVE: To screen Vietnamese medicinal plants for xanthine oxidase (XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant. METHODS: The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol. Bioassay-guided fractionation and column chromatography were used to isolate compounds. The compounds structures were elucidated by analysis of spectroscopic data, including IR, MS, and NMR. RESULTS: Three hundreds and eleven methanol extracts (CME) belonging to 301 Vietnamese herbs were screened for XO inhibitory activity. Among these plants, 57 extracts displayed XO inhibitory activity at 100 µg/mL with inhibition rates of over 50%. The extracts of Archidendron clypearia (A. clypearia), Smilax poilanei, Linociera ramiflora and Passiflora foetida exhibited the greatest potency with IC50 values below 30 µg/mL. Chemical study performed on the extract of A. clypearia resulted in the isolation of six compounds, including 1-octacosanol, docosenoic acid, daucosterol, methyl gallate, quercitrin and (-)-7-O-galloyltricetiflavan. The compound (-)-7-O-galloyltricetiflavan showed the most potent XO inhibitory activity with an IC50 value of 25.5 µmol/L. CONCLUSIONS: From this investigation, four Vietnamese medicinal plants were identified to have XO inhibitory effects with IC50 values of the methanol extracts below 30 µg/mL. Compound (-)-7-O- galloyltricetiflavan was identified as an XO inhibitor from A. clypearia with IC50 value of 25.5 µmol/L.

New flavonoid and pentacyclic triterpene from Sesamum indicum leaves.

Two new and one known compounds were isolated from the methanol extract of Sesamum indicum leaves. By means of spectroscopic methods, their structures were elucidated and identified to be 3-epibartogenic acid (1), kaempferol 3-O-[2-O-(trans-p-coumaroyl)-3-O-α-L-rhamnopyranosyl]-ß-D-glucopyranoside (2) and epigallocatechin (3). Compound 1 and 3 strongly inhibited α-amylase with the IC50 values of 146.7 and 303.9 µM, respectively, in comparison with acarbose (IC50 124.0 µM).

Suprafenacine, an indazole-hydrazide agent, targets cancer cells through microtubule destabilization.

Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule--4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G2/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK-mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3. Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our results suggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents.

Primarily opinions of the anatomy of maxillary deciduous teeth in children in Hanoi

During the stable physiological stage, the molar may be treated by root channel filling. The silver- amalgamated filling in carious cavities of 2 nd class at interproximal faces may be easily detached. It seems to be advantageous to merely fill these cavities without restoring the interproximal edges

The orodental disease in primary school ages of 8-11 in Thua town, Gia Guong district and risk factors

1. The proportion of carries to pupils in Thua town is 54.4%, in which permanent teeth carries is 5.9% and periodontosis is 83.3%. 2. There is no statistical difference among the proportions of carries, permanent teeth carries and periodontosis distinguished by sex and ages. 3. There is a relation between daily tooth, (as well as time of brushing, number of teething everyday) and the propotion of carious and periodontosis. 4. There is a clear relation between frequently candy eating and carious as well as periodontosis. 5. Based on the relation between knowledge on reason of carries as well as the the method of precaution and carries/ periodontosis, we can suggest that pupil having good education on carries precaution will be able to avoid carries as well as periodontosis.

Prevalence of orodental diseases in pupils with ages of 12 in secondary schools, Cau Giay district and risk factors

We undertake this study to create a base for expanding the school dental program in the whole country of Vietnam, firstly in Hanoi capital and Cau Giay district just established. Our research scope is of 9,512 pupils selected accidentally from several Secondary schools located in Cau giay district in Feb 1998. Followings are the minitial results of our research: 1. The proportion of carries to 12 years old pupils in Cau Giay district is 37.9% in which there are no difference between the boys and girls. 2. The proportion of periodontosis is 77.9%, in which the boys is more than the girls with p< 0.05. 3. Eating candy and other sweets too much is a causative for carries (with OR= 5.7) and for periodontosis (with OR= 4.28) 4. Infrequent tooth brush also is a causative agent for carries (with OR = 4.58) and periodontositis (with OR=3.87)

Efficacy of cleaning the teeth by fluoride solution of 0.2% in school age for the teeth decay

1. Fluor can reduce the progression of carious diseases when SMT> 3. While the index of permanent teeth carious of 12-year-old pupils in the North of Vietnam is 0.06, Fluor has no effectiveness to reduce the progression of carious to permanent teeth, it has effectiveness only to milk teeth, (SMT= 3.5) 3. There has been already one auxiliary dentist in primary school named Quang Trung in charge of dental hygiene education, regular scalling.. for school children these achievements do not however meet the expected results we actually need.