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In this project, para‐carboxamidostilbene derivatives were synthesized using the Heck coupling reaction, confirmed through various analytical techniques such as FT‐IR, HRMS, and NMR analyses, and tested in vitro to evaluate their α‐amylase inhibitory activity. In silico molecular docking was employed to model the binding interactions of compounds with α‐amylase. Pharmacokinetic properties (ADME) and drug‐likeness were also examined. Structure activity relationship (SAR) analysis was conducted to establish the relationship between the chemical structure and α‐amylase inhibitory activity. The synthesized compounds exhibited significant α‐amylase inhibitory activity with IC50 values ranging from 15.0 to 37.5 µM in comparison with acarbose (IC50 = 30.2 ± 1.9 µM). Among them, compounds 6d–6f and 7c–7f demonstrated promising inhibitory activity. Furthermore, molecular docking studies revealed strong interactions between the studied molecules and the α‐amylase binding pocket. The drug‐likeness prediction results indicated that all synthesized compounds adhered to Lipinski's rule of five, suggesting their suitability as drug‐like molecules. Additionally, the assessment of ADMET properties indicated favorable absorption profiles, particularly in terms of human intestinal absorption (HIA). Overall, this study successfully identified several para‐carboxamidostilbene derivatives as potential α‐amylase inhibitors for the treatment of T2DM. [ABSTRACT FROM AUTHOR]

Genus Calophyllum is well-known for its phenolic constituents, especially coumarins, which have shown to have a wide range of significant biological activities. In this study, four known phenolic constituents and two triterpenoids have been isolated from the stem bark of Calophyllum lanigerum. The compounds were two pyranochromanone acids are known as caloteysmannic acid (1), isocalolongic acid (2), a simple dihydroxyxanthone, namely euxanthone (3), one coumarin named calanone (4), and two common triterpenoids, friedelin (5), and stigmasterol (6). Chromanone acids were reported for the first time in this Calophyllum species. Cytotoxic evaluations were carried out on n-hexane extract (87.14 ± 2.04 µg/mL; 81.46 ± 2.42 µg/mL) followed by the chromanone acids (1 [79.96 ± 2.39 µM; 83.41 ± 3.39 µM] & 2 [57.88 ± 2.34; 53.04 ± 3.18 µM]) against two cancerous cell lines, MDA-MB-231 and MG-63 cell lines, respectively. The results showed that all tested samples exhibited moderate cytotoxicity. [ABSTRACT FROM AUTHOR]

Mitragynine and its congeners are one of the major phytoconstituents present in Mitragyna speciosa Korth. (ketum) leaves and a well-known factor that contributes to ketum's pharmacological activities. This study describes the usage of a green extraction method to yield botanical leaf extracts of ketum. The leaf extracts were assessed for mitragynine content, total phenolic and flavonoid content, and cytotoxicities. The Ultrasound Assisted Extraction (UAE) method showed a varying dry yield of the extracts (0.22–1.92 g) that were obtained with solvents of variable polarities. However, the mitragynine content was consistent among the organic solvent extracts (7.22–9.40%). This method calls for a minimal extraction solvent volume (solid to solvent ratio, 1:30) and a shorter extraction period (20 min). Of the solvents tested, the methanolic extract showed the highest content of total phenolic (419.50 ± 2.50 GAE mg/g) and flavonoids (177.33 ± 3.00 QE mg/g). The extract was nontoxic towards kidney (HEK-293) and Chang liver (HeLa) cell lines. Analysis via UHPLC-ESI-QTOF-MS/MS made it possible to identify mitragynine congeners, such as mitragynine, paynantheine, and speciociliatine, in the leaves extract. In conclusion, the UAE method using methanol as the extraction solvent provides a noncytotoxic ketum botanical extract for future preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Genus Calophyllum from the family of Calophyllaceae is an evergreen broad-leaved tree that is endemic to Southeast Asia, especially Malaysia. They have been reported for various ethnomedicinal uses in traditional medicine. Previous studies of Malaysian Calophyllum species revealed them to be a rich source of bioactive phytoconstituents such as xanthones, coumarins, terpenoids, and chromanone acids. To date, the extracts and compounds from Malaysian Calophyllum species have shown a broad spectrum of pharmacological activities. For example, calanolide A, a coumarin isolated from Malaysian C. lanigerum, has now reached clinical development to become an anti-HIV drug. This article presents an overview of the significant phytochemical and pharmacological activities of Malaysian Calophyllum species to aid researchers in further discovery of potential benefits of various species of this genus. [ABSTRACT FROM AUTHOR]

Mitragynine, is a naturally occurring indole alkaloid that can be isolated from the leaves of a psychoactive medicinal plant. Mitragyna speciosa , also known as kratom, is found to possess promising analgesic effects on mediating the opioid receptors such as µ (MOR), δ (DOR), and κ (KOR). This alkaloid has therapeutic potential for pain management as it has limited adverse effect compared to a classical opioid, morphine. Mitragynine is frequently regarded to behave like an opioid but possesses milder withdrawal symptoms. The use of this alkaloid as the source of an analgesic candidate has been proven through comprehensive preclinical and clinical studies. The present data have shown that mitragynine is able to bind to opioid receptors, particularly MOR, to exhibit the analgesic effect. Moreover, the chemical and pharmacological aspects of mitragynine and its diastereomers, speciogynine, speciociliatine, and mitraciliatine, are discussed. It is interesting to know how the difference in stereochemical configuration could lead to the difference in the bioactivity of the respective compounds. Hence, in this review, the updated pharmacological and toxicological properties of mitragynine and its diastereomers are discussed to render a comprehensive understanding of the pharmacological properties of mitragynine and its diastereomers based on their structure–activity relationship study. [ABSTRACT FROM AUTHOR]

High fructose consumption has been linked to low‐grade inflammation and insulin resistance that results in increased intracellular 11ß‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)‐induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co‐administrations upon HFrD in rats and evaluate its potential to modulate 11β‐HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor‐kappa B (NF‐κB)‐driven inflammation, reduced c‐Jun N‐terminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β‐HSD1 towards oxidoreductase activity (IC50 value = 4.3 nM) in comparison to other HSD‐related enzymes. Inhibition of 11β‐HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein expressions of glucocorticoid receptor. In conclusion, our results underscore the most likely conceivable mechanisms exhibited by celastrol against HFrD‐induced metabolic dysregulations mainly through attenuating inflammation and insulin resistance, at least via specific inhibitions on 11β‐HSD1 activity in adipose tissues. [ABSTRACT FROM AUTHOR]

The use of lycopene as a complementary medicine for Type II diabetes mellitus (T2DM) is limited and controversial. This study evaluated the effect of lycopene intake on the changes of glycaemic status and antioxidant capacity among the T2DM patients. This case–control study involved the participation of 87 patients and 122 healthy individuals. Lycopene intake was assessed by using a food frequency questionnaire. The peripheral antioxidant capacity among the T2DM patients was evaluated. Glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were measured as indications of glycaemic status. Peripheral antioxidant capacity was significantly lower in the T2DM group. Direct positive correlations were found between the lycopene intake and peripheral antioxidant level among the T2DM patients. Contrarily, HbA1c and FPG levels decreased significantly with the higher lycopene intake. T2DM patients with a higher lycopene intake showed a greater peripheral antioxidant capacity and better glycaemic control. Lycopene may act to ameliorate oxidative stress and improve the pathophysiology of T2DM. [ABSTRACT FROM AUTHOR]

This study aimed to isolate, identify, and conduct a growth study of potential probiotics from pineapple peel (PP), watermelon peel (WP), and banana peel (BP). Six strains were isolated, and the growth study was conducted at 30°C at 150 rpm after 24 hr incubation. Based on colony characteristics, cell morphology, and gene sequencing, the isolates were identified as yeast strains, namely, Meyerozyma caribbica (PP) and Candida orthopsilosis (WP and BP). M. caribbica showed the highest biomass production of 2.34 g/L. Less biomass production of 2.01 and 2.18 g/L was obtained for C. orthopsilosis (WP and BP), respectively. The maximum specific growth rate in the exponential phase was 1.83 and 1.23 h−1 for C. orthopsilosis (WP and BP), followed by 1.04 hr−1 for M. caribbica, respectively. M. caribbica isolated from PP belongs to the group of potential yeast probiotics which is a good candidate for further studies to determine its probiotic properties. Novelty impact statement: Waste utilization for an economical and alternative natural source of probiotic production. The probiotic potential in yeasts has not been extensively studied before. In this study, Meyerozyma caribbica was identified from pineapple peels as a new yeast probiotic starter. M. caribbica exhibited the highest biomass production and maximum growth rate, so these essential parameters in determining the quantitative importance should be considered. [ABSTRACT FROM AUTHOR]

Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant's bioactive constituents have not yet been unveiled for most of these mechanisms. In the current study, we aim to elucidate the binding interaction of ten bioactive phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis software, Autodock 4.2. The stability of the complex with highest affinity was evaluated using MD simulation. We compared the docking analysis of these substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study identified the potential chemopreventive agent among the bioactive compounds. We also characterized the important interacting residues of protein targets which involve in the binding interaction. Results displayed that anonaine, a benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic family of proteins. [ABSTRACT FROM AUTHOR]

Celastrol, a natural triterpene from the Tripterygium wilfordii has been demonstrated to possess attributive properties to attenuate various animal models of obesity-associated conditions. The present study aimed to elucidate the putative targets of celastrol on intracellular glucose utilization and mitochondrial oxidative metabolism in the isolated quadriceps skeletal muscle of high-fat diet (HFD)-induced obese male C57BL6/J mice. Here we showed that celastrol remarkably attenuated obesity and insulin resistance through improvement of systemic glucose tolerance and insulin sensitivity. Enhanced mRNA transcription factors of key rate-limiting glycolytic and TCA cycle enzymes were observed following celastrol administration. The metabolic profiling revealed profound changes induced by celastrol administration on several key metabolites of glycolysis and tricarboxylic acid (TCA) cycle including glucose-1-phosphate, pyruvate, citrate, α-ketoglutarate, succinate and fumarate. Celastrol effectively increased mitochondrial oxidative functions via increased pyruvate dehydrogenase complex (PDC) activity and downregulated pyruvate dehydrogenase kinase 4 (PDK4) expressions. Enhanced succinate dehydrogenase (SDH) activity was noticed following celastrol co-supplementation, leading to a steady establishment of the electrochemical gradient across mitochondrial membrane for ATP production and mitochondrial biogenesis. In conclusion, the current findings accentuate the therapeutic potential of celastrol against HFD-induced obese mice via enhanced glucose utilization and mitochondrial oxidative metabolism-mediated upregulation of PDC activity in the skeletal muscle. [Display omitted] • Celastrol improved glucose tolerance and insulin sensitivity in obese mice. • Celastrol altered glycolysis and TCA cycles metabolites in the skeletal muscle. • Celastrol improved respiratory substrate utilization and mitochondrial functions. • Celastrol enhanced pyruvate dehydrogenase complex activities. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that activation of nuclear factor kappa B (NF-κB) signaling pathways is among the inflammatory mechanism involved in the development of insulin resistance and chronic low-grade inflammation in adipose tissues derived from obese animal and human subjects. Nevertheless, little is known about the roles of NF-κB pathways in regulating mitochondrial function of the adipose tissues. In the present study, we sought to investigate the direct effects of celastrol (potent NF-κB inhibitor) upon mitochondrial dysfunction-induced insulin resistance in 3T3-L1 adipocytes. Celastrol ameliorates mitochondrial dysfunction by altering mitochondrial fusion and fission in adipocytes. The levels of oxidative DNA damage, protein carbonylation and lipid peroxidation were down-regulated. Further, the morphology and quantification of intracellular lipid droplets revealed the decrease of intracellular lipid accumulation with reduced lipolysis. Moreover, massive production of the pro-inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were markedly depleted. Insulin-stimulated glucose uptake activity was restored with the enhancement of insulin signaling pathways. This study signified that the treatments modulated towards knockdown of NF-κB transcription factor may counteract these metabolic insults exacerbated in our model of synergy between mitochondrial dysfunction and inflammation. These results demonstrate for the first time that NF-κB inhibition modulates mitochondrial dysfunction induced insulin resistance in 3T3-L1 adipocytes. [ABSTRACT FROM AUTHOR]

Mitragyna speciosa Korth (kratom) is known for its psychoactive and analgesic properties. Mitragynine is the primary constituent present in kratom leaves. This study highlights the utilisation of the green accelerated solvent extraction technique to produce a better, non-toxic and antinociceptive active botanical extract of kratom. ASE M. speciosa extract had a dry yield (0.53–2.91 g) and showed a constant mitragynine content (6.53–7.19%) when extracted with organic solvents of different polarities. It only requires a shorter extraction time (5 min) and a reduced amount of solvents (less than 100 mL). A substantial amount of total phenolic (407.83 ± 2.50 GAE mg/g and flavonoids (194.00 ± 5.00 QE mg/g) were found in ASE kratom ethanol extract. The MTT test indicated that the ASE kratom ethanolic leaf extract is non-cytotoxic towards HEK-293 and HeLa Chang liver cells. In mice, ASE kratom ethanolic extract (200 mg/kg) demonstrated a better antinociceptive effect compared to methanol and ethyl acetate leaf extracts. The presence of bioactive indole alkaloids and flavonols such as mitragynine, paynantheine, quercetin, and rutin in ASE kratom ethanolic leaf extract was detected using UHPLC-ESI-QTOF-MS/MS analysis supports its antinociceptive properties. ASE ethanolic leaf extract offers a better, safe, and cost-effective choice of test botanical extract for further preclinical studies. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that adipose tissue inflammation and mitochondrial dysfunction in skeletal muscle are inextricably linked to obesity and insulin resistance. Celastrol, a bioactive compound derived from the root of Tripterygium wilfordii exhibits a number of attributive properties to attenuate metabolic dysfunction in various cellular and animal disease models. However, the underlying therapeutic mechanisms of celastrol in the obesogenic environment in vivo remain elusive. Therefore, the current study investigated the metabolic effects of celastrol on insulin sensitivity, inflammatory response in adipose tissue and mitochondrial functions in skeletal muscle of the high fat diet (HFD)-induced obese rats. Our study revealed that celastrol supplementation at 3 mg/kg/day for 8 weeks significantly reduced the final body weight and enhanced insulin sensitivity of the HFD-fed rats. Celastrol noticeably improved insulin-stimulated glucose uptake activity and increased expression of plasma membrane GLUT4 protein in skeletal muscle. Moreover, celastrol-treated HFD-fed rats showed attenuated inflammatory responses via decreased NF-κB activity and diminished mRNA expression responsible for classically activated macrophage (M1) polarization in adipose tissues. Significant improvement of muscle mitochondrial functions and enhanced antioxidant defense machinery via restoration of mitochondrial complexes I + III linked activity were effectively exhibited by celastrol treatment. Mechanistically, celastrol stimulated mitochondrial biogenesis attributed by upregulation of the adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) signaling pathways. Together, these results further demonstrate heretofore the conceivable therapeutic mechanisms of celastrol in vivo against HFD-induced obesity mediated through attenuation of inflammatory response in adipose tissue and enhanced mitochondrial functions in skeletal muscle. • Celastrol enhanced systemic insulin sensitivity and insulin-stimulated muscle glucose uptake of the diet-induced obese rats. • Celastrol attenuated inflammatory responses and macrophage polarization in adipose tissues. • Celastrol improved muscle mitochondrial functions and antioxidant defense machinery systems. • Celastrol stimulated muscle mitochondrial biogenesis by upregulating AMPK/SIRT1 signaling pathways. [ABSTRACT FROM AUTHOR]

Herbal plants are traditionally utilized to treat various illnesses. They contain phytochemicals that can be extracted using conventional methods such as maceration, soxhlet, and boiling, as well as non-conventional methods including ultrasonic, microwave, and others. Carica papaya leaves have been used for the treatment of dengue, fungal, and bacterial infections as well as an ingredient in anti-aging products. Phytochemicals analysis detected the presence of kaempferol, myricetin, carpaine, pseudocarpaine, dehydrocarpaine I and II, ferulic acid, caffeic acid, chlorogenic acid, β-carotene, lycopene, and anthraquinones glycoside. Conventional preparation by boiling and simple maceration is practical, simple, and safe; however, only polar phytochemicals are extracted. The present study aims to investigate the effects of three different non-conventional extraction techniques (ultrasonic-assisted extraction, reflux, and agitation) on C. papaya phytochemical constituents, the antioxidant capacity, and wound-healing activities. Among the three techniques, the reflux technique produced the highest extraction yield (17.86%) with the presence of saponins, flavonoids, coumarins, alkaloids, and phenolic metabolites. The reflux technique also produced the highest 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging with an IC50 value of 0.236 mg/mL followed by ultrasonic-assisted extraction (UAE) (IC50: 0.377 mg/mL) and agitation (IC50: 0.404 mg/mL). At tested concentrations (3.125 µg/mL to 500 µg/mL), all extracts do not exhibit a cytotoxicity effect on the human skin fibroblast, HSF1184. Interestingly, reflux and UAE were active fibroblast proliferators that support 85% (12.5 µg/mL) and 41% (6.25 µg/mL) better cell growth, respectively. Additionally, during the early 24 h of the scratch assay, the migration rate at 12.5 µg/mL was faster for all extracts with 51.8% (reflux), 49.3% (agitation), and 42.5% (UAE) as compared to control (21.87%). At 48 h, proliferated cells covered 78.7% of the scratch area for reflux extract, 63.1% for UAE, 61% for agitation, and 42.6% for control. Additionally, the collagen synthesis was enhanced for 31.6% and 65% after 24 and 48 h of treatment for reflux. An HPLC-MS/MS-QTOF (quadruple time-of-flight) analysis of reflux identified nine phytochemicals, including carpaine, kaempferol 3-(2G-glucosylrutinoside), kaempferol 3-(2″-rhamnosylgalactoside), 7-rhamnoside, kaempferol 3-rhamnosyl-(1->2)-galactoside-7-rhamnoside, luteolin 7-galactosyl-(1->6)-galactoside, orientin 7-O-rhamnoside, 11-hydroperoxy-12,13-epoxy-9-octadecenoic acid, palmitic amide, and 2-hexaprenyl-6-methoxyphenol. The results suggested that reflux was the best technique as compared to ultrasonic and agitation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A phytochemical investigation of the methanolic extract of Endiandra kingiana (bark) led to the isolation of four major compounds which are kingianic acid A (1), tsangibeilin B (2), kingianin A (3) and kingianin F (4). The structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The compounds were screened for their in vitro α-glucosidase inhibition activity. Among them, compounds 3-4 showed potent α-glucosidase inhibition activity with IC50 value at 11.9 ± 2.0 µM and 19.7 ± 1.5 µM, respectively. The molecular docking study found that both compounds were bound into the active site of the N-terminal of MGAM, and thus agreed with the in vitro α-glucosidase enzyme inhibition activity results. [ABSTRACT FROM AUTHOR]

Bioethanol has been produced from sugars originating from starchy staple crops such as wheat, sugarcane or corn. However, these sugar- and starch-containing feedstocks are predominantly used for food and feed, which affecting their continuous supply. In Malaysia, banana residual is the second largest agricultural waste after oil palm wastes. Banana fronds need only a milling process for the extraction of sugars to fermentation medium, and ethanol can be produced directly from juice. The sugars and minerals composition of the banana frond juice (BFJ) and the effects of BFJ concentration, addition of nitrogen sources and pH were studied. The pressed juice of the banana fronds was found to contain a total sugar of 14% with the amount of glucose (18.9 g/L), sucrose (13.29 g/L) and fructose (15.63 g/L) with total volume of 0.33 L of BFJ/kg of banana frond. The BFJ at 80% (v/v) supplemented with yeast extract at 15 g/L with optimum pH at 6.8 successfully increased the bioethanol concentration to 42.47 g/L. The optimized fermentation conditions in shake flask were scaled up to 2 L bioreactor. The bioethanol concentration that obtained in the bioreactor system was 45.75 g/L, which is 0.33 g ethanol/g sugar or 65% of the theoretical yield. The results obtained from this study showed the potential of production of sugars from BFJ for the subsequent production of bioethanol and further optimization on the parameters of bioreactor is needed to improve the bioethanol production. Image 1 • Banana frond juice contains novel renewable sugars as fermentation substrate. • Direct pressed banana frond juice contains high glucose content which was 18.9 g/L. • High bioethanol yield was obtained with yeast extract supplementation and without pH adjustment. • Banana frond juice is a new non-food and non-cellulosic substrate for bioethanol production. [ABSTRACT FROM AUTHOR]

Due to the recent emergence of drug-resistance of antidiabetic drugs and the increase in the number of diabetes cases around the world, the search for and discovery of more effective a-amylase inhibitors is of great interest. In the present study, a new series of eighteen ortho-carboxamidostilbene derivatives were synthesized via Heck coupling reaction. The structures of the synthesized compounds were identified by various spectroscopic techniques, including HREIMS, FTIR and 1D-NMR. In addition, the compounds were evaluated in vitro for their potential a-amylase inhibitory potency using acarbose as the reference drug. Compounds 5e, 5f and 6e showed remarkably moderate to good inhibitory activity with IC50 values ranging from 13.3 - 28.2 µM. These compounds showed potent IC50 values compared to the reference drug acarbose (IC50 = 30.2 ± 0.1 µM). The in silico molecular docking studies revealed the binding interactions of the most active ortho-carboxamidostilbene derivatives (5e and 6e) with binding energies of -8.7 ± 0.0 and -8.6 ± 0.2 kcal/mol, respectively. Based on the structure-activity relationship (SAR) analysis, it was established that variations in the inhibitory activities of a-amylase enzymes were attributed to distinct types of substituents at the amide group of the aryl ring A along with the number and position of methoxy groups attached to the aryl ring B. These findings highlight the a-amylase inhibitory properties of orthocarboxamidostilbene containing cyclohexane and phenyl moieties, serving as potential lead compounds in antidiabetic drug development for the treatment of type II diabetes mellitus. [ABSTRACT FROM AUTHOR]

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 IC 50 = 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 (IC 50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC 50 = 16.4 ± 0.1 μM) and α-glucosidase (IC 50 = 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., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Bioactive phenolics can be found in abundance in Calophyllum species. Phytochemical studies are carried out on the stem bark of Calophyllum recurvatum and Calophyllum andersonii , which has led to the isolation and elucidation of phytochemicals, thwaitesixanthone (1), teysmanone A (2), soulattrolide (3), calanone (4), isocalanone (5) and friedelin (6), respectively. The cytotoxic activities of compounds (2), (3), (4) and (5) as well as plant extracts were tested against HeLa Chang liver, HepG2 and HL-7702 cell lines. Phenylpyranocoumarins, teysmanone A (2) and soulattrolide (3) portrayed appreciable cytotoxicity activities at 42.57 ± 1.20 and 34.53 ± 3.41 µg/mL, respectively against HepG2 cell line comparable to the positive control, curcumin. Meanwhile, n -hexane extract from C. recurvatum exhibited cytotoxicity with the IC 50 value of 36.43 ± 0.64 and 26.25 ± 4.83 µg/mL against HeLa Chang liver and HepG2 cell lines. All the tested compounds and plant extracts displayed non-cytotoxic properties on HL-7702 cell line.

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 IC 50 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 .

Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.