Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative inquiry encompassed the isolation of phytochemical components from the bark of Kopsia teoi, followed by the assessment of their α-amylase inhibition. The phytochemical composition of the K. teoi culminated in the discovery of a pair of new indole alkaloids; which are 16-epi-deacetylakuammiline N(4)-methylene chloride (akuammiline) (1), and N(1)-methoxycarbonyl-11-methoxy-12-hydroxy-Δ14-17-kopsinine (aspidofractinine) (2), together with five known compounds i.e. kopsiloscine G (aspidofractinine) (3), akuammidine (sarpagine) (4), leuconolam (aspidosperma) (5), N-methoxycarbonyl-12-methoxy-Δ16, 17-kopsinine (aspidofractinine) (6), and kopsininate (aspidofractinine) (7). All compounds were determined via spectroscopic analyses. The in vitro evaluation against α-amylase showed good inhibitory activities for compounds 5-7 with the inhibitory concentration (IC50) values of 21.7 ± 1.2, 34.1 ± 0.1, and 30.0 ± 0.8 μM, respectively compared with the reference acarbose (IC50 = 34.4 ± 0.1 μM). The molecular docking outputs underscored the binding interactions of compounds 5-7 ranging from -8.1 to -8.8 kcal/mol with the binding sites of α-amylase. Consequently, the outcomes highlighted the anti-hyperglycemic attributes of isolates from K. teoi.
A total of five new mexicanolides (1-5), namely alliaxylines A-E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.
A new seco-A tirucallane triterpenoid named excelxylin A (1), along with two known seco-A triterpenoids (2-3), were isolated from the n-hexane extract of Dysoxylum excelsum (Spreng.) Blume ex G.Don stem bark. The structure and stereochemistry configuration of compounds 1-3 was established by NMR, IR, and HR-ESI-MS spectroscopic data analyses and comparison of their NMR data with literatures. The compounds exhibited the carbon framework for seco-A ring tirucallane triterpenoid, first reported in the Dysoxylum genus. All compounds were tested for their cytotoxicity against human cervical HeLa cells.
New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 μM) and α-glucosidase (IC50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol-1, while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol-1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.
Three new dammarane-type triterpenoids, namely elliptaglin A-C (1-3) were isolated from the stem bark of Aglaia elliptica (C.DC.) Blume along with three known derivatives, namely (20S)-hydroxydammar-24-en-3-on (4), cabralealactone (5), and E-25-hydroperoxydammar-23-en-20-ol-3-one (6). Subsequently, their chemical structures were determined using HR-ESI-MS, FTIR, 1D and 2D-NMR spectroscopic analysis as well as comparison with previous studies. The cytotoxicity activities of the isolated compounds against MCF-7 breast cancer and B16-F10 melanoma cell lines were then tested using PrestoBlue reagent. The analysis results showed that elliptaglin B (2) had the strongest activity against both cell lines with IC50 values of 60.98 and 51.83 µM, respectively.
Phytochemical investigation on the bark of E. kingiana plant afforded ten compounds, including six polyketides namely kingianin A 1, kingianin B 2, kingianin E 3, kingianin F 4, kingianin K 5 and kingianin L 6, three endiandric acids; kingianic acid A 7, tsangibeilin B 8 and endiandric acid M 9, and one sesquiterpene; daibuoxide 10. All compounds were separated as racemic mixture by recycling high-performance liquid chromatography (RHPLC), except for daibuoxide. Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. This is the first report on the presence of the sesquiterpene; daibuoxide in Endiandra genus. In vitro enzymatic bio-evaluation of the isolated compounds against α-amylase and α-glucosidase showed that 4 demonstrated the best α-amylase and α-glucosidase inhibitory activity with IC50 values of 181.54 ± 6.27 µg/mL and 237.87 ± 0.07 µg/mL, respectively. In addition, molecular docking analysis confirmed the α-amylase and α-glucosidase inhibitory activities demonstrated by 4.
In our effort to develop potent anti-hyperglycemic compounds with inhibitory activity against α-amylase and α-glucosidase, a series of novel quinoxaline-isoxazole moieties were synthesized. The novel quinoxaline-isoxazole derivatives were assessed in vitro for their anti-hyperglycemic activities on α-amylase and α-glucosidase inhibitions. The results revealed promising IC50 values compared to acarbose as a positive control for α-amylase and α-glucosidase. Among them, N-Ethyl-7-chloro-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5b showed dual inhibitory with IC50 of 24.0 µM for α-amylase and 41.7 µM for α-glucosidase. In addition, N-Ethyl-7-methoxy-3-((3-(2-chlorophenyl)isoxazol-5-yl)methoxy)quinoxalin-2-amine 5j also had dual bioactivities against α-amylase and α-glucosidase with IC50 of 17.0 and 40.1 µM, respectively. Nevertheless, two more compounds N-Ethyl-7-cyano-3-((3-phenylisoxazol-5-yl)methoxy)quinoxaline-2-amine 5e showed strong mono-inhibition for α-glucosidase with IC50 of 16.6 µM followed by N-Ethyl-7-methoxy-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5 f with IC50 of 18.6 µM. The molecular docking study for α-glucosidase inhibitor provided the binding energy ranging from 8.3 to 9.1 kcal/mol and α-amylase inhibitor showed the binding energy score at 8.4 and 8.5 kcal/mol. The dual inhibitions nature of 5b and 5j were further analyzed and confirmed via molecular dynamics including the stability of the compound, interaction energy, binding free energy, and the interaction residue analysis using the MM-GBSA approach. The results showed that compound 5j was the most potent compound. Lastly, the drug-likeness properties were also evaluated with all synthesized compounds 5a-5j and the results reveal that all potent compounds meet Lipinski's rules of five.
The Aglaia genus, a member of the Meliaceae family, is generally recognized to include a number of secondary metabolite compounds with diverse structures and biological activities, including triterpenoids. Among the members of this genus, Aglaia cucullata has been reported to have unique properties and thrives exclusively in mangrove ecosystems. This plant is also known to contain various metabolites, such as flavaglines, bisamides, and diterpenoids, but there are limited reports on the isolation of triterpenoid compounds from its stem bark. Therefore, this research attempted to isolate and elucidate seven triterpenoids belonging to dammarane-type (1-7) from the stem bark of Aglaia cucullata. The isolated compounds included 20S,24S-epoxy-3α,25-dihydroxy-dammarane (1), dammaradienone (2), 20S-hydroxy-dammar-24-en-3-on (3), eichlerianic acid (4), (20S,24RS)-23,24-epoxy-24-methoxy-25,26,27-tris-nor dammar-3-one (5), 3α-acetyl-cabraleahydroxy lactone (6), and 3α-acetyl-20S,24S-epoxy-3α,25-dihydroxydammarane (7). Employing spectroscopic techniques, the chemical structures of the triterpenoids were identified using FTIR, NMR, and HRESITOF-MS. The cytotoxic activity of compounds 1-7 was tested with the PrestoBlue cell viability reagent against MCF-7 breast cancer, B16-F10 melanoma, and CV-1 normal kidney fibroblast cell lines. The results displayed that compound 5 had the highest level of bioactivity compared to the others. Furthermore, the IC50 values obtained were more than 100 μM, indicating the low potential of natural dammarane-type triterpenoids as anticancer agents. These findings provided opportunities for further studies aiming to increase their cytotoxic activities through semi-synthetic methods.
This paper reports the optical properties of zinc oxide nanofilm fabricated by using organic natural products from Salvia officinalis leaves (SOL) extract and discusses the effect of the nanocrystal (NC) structure (nanoyarn and nanomat-like structure) on nanofilm optical properties. The surface-active layer of the nanofilm of ZnO nanoparticles (ZnO NPs) was passivated with natural organic SOL leaves hydrothermally, then accumulated on zinc oxide nanorods (ZnO NRs). The nanofilms were fabricated (with and without PEO) on glass substrate (at 85 °C for 16 h) via chemical solution deposition (CSD). The samples were characterized by UV-vis, PL, FESEM, XRD, and TEM measurements. TEM micrographs confirmed the nucleation of ZnO NPs around 4 nm and the size distribution at 1.2 nm of ZnO QDs as an influence of the quantum confinement effect (QCE). The nanofilms fabricated with SOL surfactant (which works as a capping agent for ZnO NPs) represent distinct optoelectronic properties when compared to bulk ZnO. FESEM images of the nanofilms revealed nanoyarn and nanomat-like structures resembling morphologies. The XRD patterns of the samples exhibited the existence of ZnO nanocrystallites (ZnO NCs) with (100), (002), and (101) growth planes. The nanofilms fabricated represented a distinct optical property through absorption and broad emission, as the optical energy band gap reduced as the nanofilms annealed (at 120 ℃). Based on the obtained results, it was established that phytochemicals extracted from organic natural SOL leaves have a distinct influence on zoic oxide nanofilm fabrication, which may be useful for visible light spectrum trapping. The nanofilms can be used in photovoltaic solar cell applications.
Two undescribed sesquiterpenoids, namely dysoticans A and B, and three undescribed sesquiterpenoid dimers, namely dysoticans C-E, together with six analogs, were isolated from the stem bark of Dysoxylum parasiticum (Osbeck) Kosterm. (Meliaceae), growing in West Java, Indonesia. Their structures were elucidated based on extensive spectroscopic analysis and theoretical simulations of ECD spectra and 13C NMR shifts. Dysoticans A and B possessed undescribed cadinanes with minor modifications, while C and D featured unprecedented pseudo-sesquiterpenoid dimers through O-ether linkages of cadinanes and guaianes, respectively. Dysotican E was also characterized as the true-sesquiterpenoid dimer featuring eudesmane-germacrene hybrid framework from the Meliaceae family. Furthermore, A-C and E showed moderate activities against the human breast cancer MCF-7 and cervical cancer HeLa cell lines with IC50 values ranging from 22.15 to 45.14 μM. D selectively exhibited significant cytotoxicity against the HeLa cell line with an IC50 value of 13.00 ± 0.13 μM.
Two new azadirone-type limonoids, namely lasiocarpine A (1) and lasiocarpine B (2) were isolated from the fruit of Chisocheton lasiocarpus along with three known limonoids (3-5). UV, IR, one- and two- dimensional NMR, and mass spectrometry were used to determine the chemical structure of the isolated compounds. Furthermore, their cytotoxic activity against breast cancer cell line MCF-7 was evaluated using PrestoBlue reagent. From these compounds, lasiocarpine A (1) showed the strongest activity with an IC50 value of 43.38 μM.
Chisocarpene A (1) is a new tirucallane-type triterpenoid together with odoratone (2) and 24-methylenecycloartanol (3), isolated from the stem bark of Chisocheton lasiocarpus. The chemical structures of compounds 1-3 were elucidated through a detailed analysis of their spectroscopic data (IR, MS, 1 D, and 2 D NMR). The isolated compounds were evaluated for cytotoxic activity against the MCF-7 breast cancer cell line using a resazurin-based assay. Compound 1 showed the most potent activity (IC50 26.56 ± 1.01 µM) and was two-fold more active than the positive control.
The Heck cross-coupling reaction is a well-established chemical tool for the synthesis of unsaturated compounds by formation of a new C-C bond. In this study, 1,3-diarylpropene derivatives, designed as structural analogues of stilbenoids and dihydrostilbenoids, were synthesised by the palladium-catalysed reactions of 2-amidoiodobenzene derivatives with either estragole or eugenol. The products were obtained with high (E) stereoselectivity but as two regioisomers. The ratios of isomers were found to be dependent on the nature of the allylbenzene partner and were rationalised by electronic effects exercising a determining influence in the β-hydride elimination step. In addition, the cytotoxic effects of all the Heck reaction products were evaluated against MCF-7 and MDA-MB-231 human breast cancer cells, with unpromising results. Among all, compound 7d exhibited weak cytotoxic activity towards MCF-7 cell lines with IC50 values of 47.92 µM in comparison with tamoxifen and was considered to have general toxicity (SI value < 2).
The non-complexity of tennis, coupled with its health benefits, renders it appealing and encourages varying competitions at different levels of age, gender, and expertise. However, the rapid increase in the participation rates witnesses a surge in injury occurrences, prompting the need for in-depth analysis to facilitate immediate intervention. We employed a media content analysis technique in which tennis-associated articles published in the last 5 years were examined. A total of 207 news reports were gathered and screened for analysis. Subsequently, 71 articles were excluded from the study due to content duplications or summary updates of existing news articles, while 23 news articles were also excluded from the study due to inappropriateness. Finally, 113 news reports directly related to injury in tennis were coded and analyzed. We examined various types of injuries reported from the screened articles with respect to their status (fresh, recurrent, and recovery) across expertise levels i.e., elite, or amateur. Similarly, the incidence of injury occurrences based on the types of tournaments the players engage in was also investigated. A chi-square analysis was employed to achieve the objectives of the study. Occurrences of tennis-associated injuries are disseminated across expertise levels [ χ ( 18 ) 2 = 16.542; p = 0.555], with knee, hip, elbow, and shoulder injuries being highly prevalent in both elite and amateur players. Nevertheless, it was noted that elite players suffered a staggering 72.60% of injury-related problems, while amateur players sustained 27.40% of injuries. Moreover, the status of injury spreads based on types of tournaments [ χ ( 4 ) 2 = 3.374; p = 0.497], with higher occurrences of fresh and recurrent injuries, while low recovery rates were observed. The findings further demonstrated that injuries are sustained regardless of tournament types [ χ ( 36 ) 2 = 39.393; p = 0.321]. However, most of the injuries occurred at international tournaments (85%). Whereas, only 5.30% of the injuries occurred at national/regional tournaments while 9.70% were unidentified. It could be deduced from the findings of this investigation that elite players are more prone to injuries compared with amateur players. Furthermore, the most common tennis-related injuries affect the lower, trunk, and upper regions of the body, respectively. A large number of the reported tennis injuries are fresh and recurrent, with a few recoveries. The international tennis tournaments are highly attributed to injury occurrences as opposed to the national/regional tournaments. The application of the media-based data mining technique is non-trivial in projecting injury-related problems that could be used to facilitate the development of an injury index peculiar to the tennis sport for prompt intervention.
A total of fourteen pyrazoline derivatives were synthesized through cyclo-condensation reactions by chalcone derivatives with different types of semicarbazide. These compounds were characterized by IR, 1D-NMR (1H, 13C and Distortionless Enhancement by Polarization Transfer - DEPT-135) and 2D-NMR (COSY, HSQC and HMBC) as well as mass spectroscopy analysis (HRMS). The synthesized compounds were tested for their antituberculosis activity against Mycobacterium tuberculosis H37Ra in vitro. Based on this activity, compound 4a showed the most potent inhibitory activity, with a minimum inhibitory concentration (MIC) value of 17 μM. In addition, six other synthesized compounds, 5a and 5c-5g, exhibited moderate activity, with MIC ranges between 60 μM to 140 μM. Compound 4a showed good bactericidal activity with a minimum bactericidal concentration (MBC) value of 34 μM against Mycobacterium tuberculosis H37Ra. Molecular docking studies for compound 4a on alpha-sterol demethylase was done to understand and explore ligand-receptor interactions, and to hypothesize potential refinements for the compound.
A new antimalarial sterol, kaimanol (1), along with a known sterol, saringosterol (2) was isolated from the Indonesian Marine sponge, Xestospongia sp. The chemical structure of the new compound was determined on the basis of spectroscopic evidences and by comparison to those related compounds previously reported. Isolated compounds, 1 and 2 were evaluated for their antiplasmodial effect against Plasmodium falciparum 3D7 strains. Compounds 1 and 2 exhibited antiplasmodial activity with IC50 values of 359 and 0.250 nM, respectively.
A study was carried out to determine the effectiveness of lignin, extracted from oil palm (Elaeis guineensis) biomass as water-in-oil (W/O) emulsifying agent. To achieve this goal, soda lignin (SL) was extracted via soda pulping process and a series of nanosized soda lignin (NSL) were prepared using homogenizer at three different speed i.e. 10,400 rpm (NSL 10), 11,400 rpm (NSL 11) and 12,400 rpm (NSL 12) for one hour. All prepared samples were characterized by FT-IR, UV-Vis spectroscopy, thermogravimetric analysis (TGA), zeta potential analyser, Transmission Electron Microscope (TEM) and Extreme High Resolution Field Emission Scanning Electron Microscope (XHR-FESEM). The result of FTIR showed that there is no prominent change occurred in spectra of all samples while a good stability was reflected by TGA curves. The percentage of creaming index and visual observations of all samples demonstrated that NSL 12 and dosage 2 g (out of 1 g, 1.5 g and 2 g) were found to be the best among all samples. Furthermore, the results of IFT indicate that NSL 12 was proven to be more stable than the commercial product. Therefore, NSL 12 is selected for toxicological studies and was found safe in both, in vitro and in vivo studies.
A series of 2-methoxypyridine-3-carbonitrile (5a-i)-bearing aryl substituents were successfully synthesized in good yields by the condensation of chalcones (4a-i) with malononitrile in basic medium. The condensation process, in most cases, offers a route to a variety of methoxypyridine derivatives (6a-g) as side products in poor yields. All new compounds were fully characterized using different spectroscopic methods. Mass ESI-HMRS measurements were also performed. Furthermore, these compounds were screened for their in vitro cytotoxicity activities against three cancer cell lines; namely, those of the liver (line HepG2), prostate (line DU145) and breast (line MBA-MB-231). The cytotoxicity assessment revealed that compounds 5d, 5g, 5h and 5i exhibit promising antiproliferative effects (IC50 1-5 µM) against those three cancer cell lines.
Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
Many studies have shown the effectiveness of educational modules on increasing colorectal cancer screening uptake at individual level but not adjusted for potential clustering effect such as workplace. Longitudinal studies on workplace colorectal cancer screening require a series of analysis under different conditions due to heterogeneity of workplace population. To achieve this, a sensitivity analysis based on Generalized Estimating Equations was conducted to determine the robustness of the predictive performance of health education module in increasing screening uptake. Materials and Method: A parallel, single blind, cluster randomized trial was conducted among 15 organizations in Kuantan, Pahang. Intervention group received a complex Health Education Module comprising of group education, practical session on fecal occult blood test usage and WhatsApp group follow-up, while control group received standard colorectal cancer screening brochure. Sensitivity analyses using intention to treat analysis with interaction term, compatibility term, behavioral intention term and key assumption term were performed. Data were imputed and analysed using generalized estimating equation with IBM SPSS version 23. Pooled adjusted odds ratio was calculated using random effect model with inverse variance weighting using RevMan version 3.5. Results: A total of 166 participants from 15 organizations were recruited in the study. Intervention and control group were comparable at baseline (P>0.05). Health Education Module given in intervention group significantly increased the uptake of FOBT by nearly 5 times compared to control group in sensitivity analyses (pooled adjusted OR=4.60, 95% CI=2.65-7.99, I2=47%, P