Inhibitory effect of gallic acid from Thunbergia mysorensis against α-glucosidase, α-amylase, aldose reductase and their interaction: Inhibition kinetics and molecular simulations.

In this exploration, we assessed the antihyperglycaemic properties of methanol extract of flowers of Thunbergia mysorensis (MeT) against α-glucosidase, α-amylase and aldose reductase enzymes for the effective management of postprandial hyperglycemia. Hyperglycemia occurs when the body lacks enough insulin or is unable to correctly utilize it. MeT inhibited both the carbohydrate digestive enzymes (α-glucosidase and α-amylase) and aldose reductase, which are vital for the therapeutic control of postprandial hyperglycaemia. MeT was also found to have significant antioxidant activity. Using several spectroscopic approaches, the primary active component found in MeT was identified as gallic acid. With low Ki values, gallic acid significantly inhibited α-glucosidase (30.86 µg/mL) and α-amylase (6.50 µg/mL). Also, MeT and gallic acid both inhibited aldose reductase effectively, corresponding to an IC50 value of 3.31 and 3.05 µg/mL. Our findings imply that the presence of polyphenol compounds (identified via HPLC analysis) is more likely to be responsible for the antihyperglycaemic role exhibited by MeT via the inhibition of α-glucosidase and the polyol pathway. Further, gallic acid interacted with the key residues of the active sites of α-glucosidase (-6.4 kcal/mol), α-amylase (-5.8 kcal/mol) and aldose reductase (-5.8 kcal/mol) as observed in the protein-ligand docking. It was also predicted that gallic acid was stable inside the binding pockets of the target enzymes during molecular dynamics simulation. Overall, gallic acid derived from MeT via bioassay-guided isolation emerges as a natural antidiabetic drug and can be taken into in vivo and clinical studies shortly.Communicated by Ramaswamy H. Sarma.

DNA aptamer selection and detection of marine biotoxin 20 Methyl Spirolide G.

This study reports the selection of DNA aptamer for the detection of 20 Methyl Spirolide G (SPXG). After 10 rounds of selection, theenriched pool of aptamers specific to SPXGwas cloned, sequenced and clustered into seven families based onsimilarity. Three sequences SPX1, SPX2 and SPX7, each belonging to different clades were further evaluated for their binding affinity. Surface plasmonresonancestudies determined the highest affinity KDof 0.0345x10-8 M for aptamer SPX7. A label-free microscale thermophoresis-based aptasensing using SPX7 with highest affinity, indicated a linear detection range from 1.9 to 125000 pg/mL (LOD = 0.39 pg/mL; LOQ = 1.17 pg/mL). Spiking studies in simulated contaminated samples of mussel and scallop indicated recoveries in the range of 86 to 108%. Results of this study indicate the successful development of an aptamer for detection of SPXG at picogram levels. It also opens up avenues to develop other sensing platforms for detection of SPXG using the reported aptamer.

Synthesis, characterization and anti-inflammatory properties of karanjin (Pongamia pinnata seed) and its derivatives.

Karanja (Pongamia pinnata) is a medicinal tree used in the Indian traditional ayurvedic system for treating several ailments. The seeds contain a unique furano-flavonoid karanjin, which has shown to possess many medicinal properties. Its usage at the clinical level is affected due to poor solubility and absorption. In the present investigation, molecular modifications of karanjin were attempted and evaluated their effect on anti-inflammatory activity. Firstly, Karanja ketone was obtained from karanjin by hydrolysis, and it was converted into karanja ketone oxime. The oxime undergoes Beckmann rearrangement and cyclized to yield furano benzoxazole (karanja oxazole). The new derivatives were purified with >95% purity (HPLC) and spectrally characterized (HR-MS, FTIR, and NMR). Among the test compounds, karanja ketone oxime exhibited higher antioxidant activity with an IC50 value of 360 µg/ml (DPPH). Soy lipoxygenase-1 (LOX-1) inhibitory activity of oxime was higher (IC50 = 65.4 µM) than other compounds. Fluorescence studies showed that oxime had higher quenching capacity with a Qmax of 76.3% and a binding constant of 0.9 × 105 M-1 for soy LOX-1. In-silico interaction studies showed that karanja ketone oxime had the least binding energy of -5.76 kcal/mol with LOX-1 by forming two hydrogen bonds with hydrophobic amino acids Leu 390 and Gly 392. The compounds were evaluated for their acute anti-inflammatory activity by the paw and ear edema in the rat model. Karanjin inhibits paw edema and ear edema by 34.13% and 51.13%, respectively, whereas the derivatives inhibited by 45-57 % and 70-76.8%. This study reports a rational approach to synthesize karanjin derivatives with considerable anti-inflammatory properties, both in-vitro and in-vivo.

Effects of ultrasound-assisted heating on aroma profile, peptide structure, peptide molecular weight, antioxidant activities and sensory characteristics of natural fish flavouring.

This study deals with the production of natural fish flavouring using ultrasound-assisted heating process. The effect of ultrasound pretreatment at different amplitudes (0, 15, 30, and 45%) on the Maillard reaction rate, antioxidant activities, flavour profile, and sensory characteristics of fish flavouring was investigated. Results showed that sonication markedly accelerated the Maillard reaction (MR) rate, as evidenced by the modification of peptide structure, a decrease in pH value, free amino acid content coupled with a rise in browning intensity. Also, ultrasound pretreatment significantly enhanced the antioxidant activities of fish flavouring (p ≤ 0.05). Moreover, sonication increased the type and content of aroma compounds significantly. Sensory analysis revealed that ultrasound pretreatment increased the fish-like and toasty aroma as well as umami and mouthfulness attributes coupled with the reduction of the bitter taste of the fish flavouring. This result was consistent with the GC-MS, electronic nose, cluster, and Partial Least Squares Regression (PLSR) analyses, which clearly showed that ultrasound pretreatment enhanced the fish-like aroma, which was associated with the increase in aldehydes, ketones, alcohols, thiophenes, pyrazine, and furans contents. Thus, it could be concluded that ultrasound pretreatment, coupled with the thermal process, could be a promising process for the production of natural fish flavouring with higher antioxidant activities.

Synthesis, antibacterial and antimutagenic activity of zerumbone-bicarbonyl analogues.

Synthesis of new zerumbone-bicarbonyl analogues by SeO2 oxidation is reported. Selective oxidation of methyl at C-13 to an aldehyde and a ketone with exo-cyclic double bond between C-13 and C-6 in zerumbone has been recognized. Both these compounds have an additional conjugated-carbonyl-functionality. They exhibited significantly higher antimutagenic activity than zerumbone against Salmonella tester strains. They are more active against Gram positive bacteria than Gram negative bacteria; however zerumbone showed highest activity against E. coli, whereas its derivatives were least effective against E. coli.

Synthesis and quorum sensing inhibitory activity of key phenolic compounds of ginger and their derivatives.

Phenolic components of ginger (Zingiber officinale Roscoe) viz. [6]-gingerol, [6]-shogaol and zingerone exhibited quorum sensing inhibitory activity (QSI) against Chromobacterium violaceum and Pseudomonas aeruginosa. The inhibitory activity of all the compounds was studied by zone inhibition, pyocyanin, and violacein assay. All the compounds displayed good inhibition at 500ppm. [6]-Azashogaol, a new derivative of [6]-shogaol has been synthesized by Beckmann rearrangement of its oxime in the presence of ZnCl2. The structure elucidation of this new derivative was carried out by 1D ((1)H NMR and (13)C NMR) and 2D-NMR (COSY, HSQC and NOESY) spectral studies. This compound showed good QSI activity against P. aeruginosa. An isoxazoline derivative of [6]-gingerol was prepared and it exhibited good QSI activity. Present study illustrated that, the phenolic compounds of ginger and their derivatives form a class of compounds with promising QSI activity.

Antibacterial and antimutagenic activities of novel zerumbone analogues.

Zerumbone, the key constituent of Zingiber zerumbet Smith, is a very important bioactive phytochemical. Two new compounds viz. azazerumbone 1 and azazerumbone 2 were synthesised by ZnCl2-catalysed Beckmann rearrangement of the zerumbone oxime. The structure elucidation of these analogues of zerumbone was carried out by 1D ((1)H NMR and (13)C NMR) and 2D-NMR (COSY, HSQC and NOESY) spectral analysis. Studies on the antibacterial activity established that azazerumbone 2 had better activity than zerumbone. Among the tested bacteria, Bacillus cereus was the most sensitive and Yersinia enterocolitica was found to be the most resistant. These compounds exhibited strong protection against sodium azide induced mutagenicity of Salmonella typhimurium strains TA 98 and TA 1531. Azazerumbone 2 showed better antibacterial and antimutagenic activity than azazerumbone 1. The antibacterial and antimutagenic activities exhibited by zerumbone and its analogues demonstrate their potential for use as nutraceuticals and in food preservation.

Synthesis of amino acid conjugates of tetrahydrocurcumin and evaluation of their antibacterial and anti-mutagenic properties.

Tetrahydrocurcumin (THC), the hydrogenated and stable form of curcumin, exhibits physiological and pharmacological activities similar to curcumin. A protocol has been developed for the synthesis of novel conjugates of THC with alanine (2a), isoleucine (2b), proline (2c), valine (2d), phenylalanine (2e), glycine (2f) and leucine (2g) in high yields (43-82%). All the derivatives of THC exhibited more potent anti-microbial activity than THC against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Yersinia enterocolitica. The MIC values of the derivatives were 24-37% of those for THC in case of both gram-positive and gram-negative bacteria. Derivatives 2g and 2d exhibited maximum anti-mutagenicity against Salmonella typhimurium TA 98 and TA 1538, respectively at a low concentration of 313 µg/plate, with comparable activity for THC evident only at 3750 µg/plate. These results clearly demonstrated that the conjugation of THC at the phenolic position with amino acids led to significant improvement of its in vitro biological attributes.

Synthesis of quinoline derivatives of tetrahydrocurcumin and zingerone and evaluation of their antioxidant and antibacterial attributes.

Tetrahydrocurcumin (THC, 1) and zingerone (2) are biologically active molecules originating from the important spices turmeric and ginger, respectively. Novel quinoline derivatives of THC and zingerone have been synthesised by an efficient protocol involving their reaction with substituted 2-aminobenzophenones and 2-aminoacetophenone. Radical-scavenging activities (RSA) of THC, zingerone and their quinoline derivatives were evaluated. The amino-substituted quinoline derivative of THC, 1e, showed antioxidant activity superior to those of 1 and 1a. Derivatives 1b, 1c, 1d and 1f exhibited relatively lower RSA at equimolar concentrations (∼50-55 µmol). A similar trend was also seen in zingerone (2) and its derivatives (2a-2e), with 2e displaying the best RSA. Derivatives of THC (1a-1f) showed stronger antimicrobial activity than THC (1) against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica. Also, derivatives of zingerone (2b-2e) exhibited lower minimum inhibitory concentrations (MIC) values than zingerone (2) and its derivative, 2a for both Gram-positive and Gram-negative bacteria. The molecules may have potential pharmacological applications.

In vivo growth inhibitory and anti-angiogenic effects of synthetic novel dienone cyclopropoxy curcumin analogs on mouse Ehrlich ascites tumor.

In the present study, four novel dienone cyclopropoxy curcumin analogs 1a-4a were synthesized by nucleophillic substitution reaction with cyclopropyl bromide. The tumor inhibitory and anti-angiogenic effects of the synthetic compounds were studied on mouse Ehrlich ascites tumor (EAT) in vivo. The compounds 1a-4a increased the life span (% ILS) of EAT bearing mice with corresponding significant reduction in ascites volume and cell number and induced apoptotic bodies in EAT cells. Anti-angiogenic studies of the compounds demonstrated significant reduction of microvessel density (MVD) in the peritoneum wall sections of mice and induced avascular zone in CAM model. Our findings demonstrate that the tumor growth inhibitory effects of synthetic dienone cyclopropoxy curcumin analogs 1a-4a could be mediated by promoting apoptosis and inhibiting tumor angiogenesis. However, the compounds need to be explored further to assess its clinical relevance.

Direct conversion of tert-beta-bromo alcohols to ketones with zinc sulfide and DMSO.

tert-Beta-bromo alcohols, derived from simple monoterpene hydrocarbons, react with zinc sulfide in dimethyl sulfoxide to afford saturated ketones as the major and hydroxy ketones as the minor products. The reaction involves initial nucleophilic attack by DMSO on the carbon attached to the halogen, which is assisted by electrophilic zinc sulfide. Subsequent Kornblum type oxidation yields the alpha-hydroxy ketone. On the other hand, abstraction of proton beta to the hydroxyl group followed by an attack of the neighboring hydroxyl moiety on the sulfur of the dimethylsulfoxonium intermediate and its subsequent collapse yields an enol, which tautomerizes to a saturated ketone. The latter pathway is predominantly followed.