In an effort to design and synthesize a new class of α-glucosidase inhibitor, we synthesized benzothiazole hybrid having benzohydrazide moiety (5). Compound 5 was reacted with various substituted aryl aldehyde to generate a small library of compounds 6-35. Synthesis of compounds was confirmed by the spectral information. These compounds were screened for their α-glucosidase activity. They showed a varying degree of α-glucosidase inhibition with IC50 values ranging between 5.31 and 53.34 μM. Compounds 6, 7, 9-16, 19, 21-30, 32-35 showed superior activity as compared to standard acarbose (IC50 = 906 ± 6.3 μM). This has identified a new class of α-glucosidase inhibitors. The predicted physico-chemical properties indicated the drug appropriateness for most of these compounds, as they obey Lipinski's rule of five (RO5). A hybrid B3LYP density functional theory (DFT) was employed for energy, minimization of 3D structures for all synthetic compounds using 6-311 + G(d,p) basis sets followed by molecular docking to explore their interactions with human intestinal C- and N-terminal domains of α-glucosidase. All compounds bind to the prospective allosteric site of the C- terminal domain, and consequently, may be considered as mixed inhibitors. It was hypothesized that both the dipole moment and H-bond interactions govern the biological activation of these compounds.
Benzothiazole analogs (1-20) have been synthesized, characterized by EI-MS and (1)H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4±0.10 to 34.43±2.10μM when compared with standard thiourea (IC50 19.46±1.20μM). Among the series seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N-phenylthiourea 20 with all substituted phenyl derivatives (1-18) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking.
The objective of this study was to evaluate the effects of solid-to-solvent ratio (1:5. 1:10, 1:15 and 1:20) on the extraction of phenolic compounds (TPC and TFC) and antioxidant capacity (ABTS and DPPH radical scavenging capacity) of P. niruri. Solid-to-solvent ratio showed a significant effect for both phenolic compounds (TPC and TFC) and antioxidant capacity (ABTS and DPPH radical scavenging capacity) with 1:20 was the condition for extracting the highest of phenolic compounds (TPC and TFC) with a value of 5788.7 mg GAE/100 g DW and 1906.5 mg CE/100 g DW, respectively and exhibited high antioxidant capacities (ABTS and DPPH radical scavenging capacities) with a value of 0.820 mM and 1.598 mM, respectively among the four levels studied. TPC was positively and significantly correlated with ABTS and DPPH (r=0.999 and r=0.999) under the effects of solid-to-solvent ratio as compared to TFC, positively and strongly correlated (r=0.865 and r=0.868) with ABTS and DPPH.
Due to the great biological importance of β-glucuronidase inhibitors, here in this study, we have synthesized a library of novel benzothiazole derivatives (1-30), characterized by different spectroscopic methods and evaluated for β-glucuronidase inhibitory potential. Among the series sixteen compounds i.e.1-6, 8, 9, 11, 14, 15, 20-23 and 26 showed outstanding inhibitory potential with IC50 value ranging in between 16.50 ± 0.26 and 59.45 ± 1.12 when compared with standard d-Saccharic acid 1,4-lactone (48.4 ± 1.25 µM). Except compound 8 and 23 all active analogs showed better potential than the standard. Structure activity relationship has been established.
The optical properties of a series of side chain liquid crystalline polymers (P1-P3) containing azo-benzothiazole mesogen with different terminal substituents (-H, -CH3 and -OCH2CH3) in four organic solvents of varying polarity have been investigated by absorption and fluorescence spectral analysis. Solvatochromic studies of P1-P3 did not show any regular variation on the absorption and emission intensities with changing the polarity of solvent. Theoretical studies were performed based on different solvent correlation methods such as Dimroth-Reichardt and Kamlet-Taft methods to investigate the solute-solvent interactions. Both absorption and emission maxima of investigated polymers were bathochromically shifted with the replacement of sixth position hydrogen atom by electron donating groups in benzothiazole moiety. The emission intensities of the studied polymers showed decreasing trend with increasing temperature.
Central composite design of response surface methodology (RSM) was employed to optimize the extraction time (X 1 : 99.5-290.5 min) and temperature (X 2 : 30.1-54.9 °C) of Schizophyllum commune aqueous extract with high antioxidant activities and total phenolic content (TPC). Results indicated that the data were adequately fitted into four second-order polynomial models. The extraction time and temperature were found to have significant linear, quadratic and interaction effects on antioxidant activities and TPC. The optimal extraction time and temperature were: 290.5 min and 35.7 °C (DPPH(•) scavenging ability); 180.7 min and 41.7 °C (ABTS(•+) inhibition ability); 185.2 min and 42.4 °C (ferric reducing antioxidant power, FRAP); 290.5 min and 40.3 °C (TPC). These optimum conditions yielded 85.10%; 94.31%; 0.74 mM Fe(2+) equivalent/100 g; 635.76 mg gallic acid equivalent/100 g, respectively. The yields of antioxidant activities and TPC obtained experimentally were close to its predicted values. The establishment of such model provides a good experimental basis employing RSM for optimizing the extraction time and temperature on antioxidants from S. commune aqueous extract.
We evaluated the phenolic content and antioxidant capacities of pod and seed extracts (in methanol, ethanol, and water) of an underutilized legume, Clitoria fairchildiana (Howard). The antioxidant capacity of the extracts was determined using the ferric reducing antioxidant potential assay, and the free radical-scavenging capacity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical-scavenging and ABTS assays. In addition, the total flavonoids, flavonols, and tannin contents were also determined. Overall, the methanol extracts of the pod contained high concentration of phenolics and showed high antioxidant capacities compared to seed extracts. In addition, a positive correlation was found between total phenol and tannin versus antioxidant capacity. Results of the present study indicate pods and seeds of C. fairchildiana to possess rich amount of natural antioxidants, and can be further explored for their possible use as a natural additive in food or in pharmaceutical industries.
Nypa fruticans Wurmb. is one of the important underutilized fruit of Malaysia, which lacks scientific attention. Total phenolics, flavonoid content, and antioxidant capacities from endosperm extracts of Nypa fruticans (unripe and ripe fruits) were evaluated. Endosperm extract of unripe fruits (EEU) exhibited the highest phenolics (135.6 ± 4.5 mg GAE/g), flavonoid content (68.6 ± 3.1 RE/g), and antioxidant capacity. Free radical scavenging capacity of EEU as assessed by 2-2'-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid (ABTS) and 1,1-diphenyl-2-picryl hydrazyl (DPPH) radicals showed inhibitory activity of 78 ± 1.2% and 85 ± 2.6%, respectively. Beta carotene bleaching coefficient of EEU was higher (2550 ± 123), when compared to endosperm extract of ripe fruits (1729 ± 172). Additionally, EEU exhibited high antioxidant capacity by phosphomolybdenum method and ferric reducing antioxidant power values. Eight phenolic compounds from Nypa fruticans endosperm extracts were identified and quantified by ultra-high-performance liquid chromatography. Chlorogenic acid, protocatechuic acid, and kaempferol were the major phenolic compounds. Thus this fruit could be used as a potential source of natural antioxidant.
A central composite design of response surface methodology (RSM) was employed to optimize the extraction time (X1: 266.4-393.6 min) and temperature (X2: 42.9-57.1°C) of Pleurotus ostreatus aqueous extract with high antioxidant activities, namely DPPH radical-scavenging activity, ABTS radical cation inhibition, and ferric reducing/antioxidant power, as well as total phenolic content (TPC). Results showed that the data were adequately fitted into four second-order polynomial models developed by RSM. The extraction time and temperature were found to have significant quadratic effects on antioxidant activities and TPC. The optimal extraction time and temperature were 282.3 min and 42.9°C (DPPH), 393.6 min and 42.9°C (ABTS), 340.4 min and 49.8°C (FRAP), and 347.6 min, 49.7°C (TPC), with corresponding yields of 53.32%, 73.20%, 37.14 mM Fe2+ equivalents/100 g, and 826.33 mg gallic acid equivalents/100 g, respectively. These experimental data were close to their predicted values. The establishment of such a model provides a good experimental basis for employing RSM to optimize the extraction time and temperature for high antioxidant activities from P. ostreatus.
Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objective of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 μM compared to that of the standard drug, prednisolone <1.5 μM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 μM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 μM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 μg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P<0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 μM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases.
Antioxidant properties of crude extract, partition extract, and fermented medium from Dendrobium sabin (DS) flower were investigated. The oven-dried DS flower was extracted using 100% methanol (w/v), 100% ethanol (w/v), and 100% water (w/v). The 100% methanolic crude extract showed the highest total phenolic content (40.33 ± mg GAE/g extract) and the best antioxidant properties as shown by DPPH, ABTS, and FRAP assays. A correlation relationship between antioxidant activity and total phenolic content showed that phenolic compounds were the dominant antioxidant components in this flower extract. The microbial fermentation on DS flower medium showed a potential in increasing the phenolic content and DPPH scavenging activity. The TPC of final fermented medium showed approximately 18% increment, while the DPPH of fermented medium increased significantly to approximately 80% at the end of the fermentation. Dendrobium sabin (DS) flower showed very good potential properties of antioxidant in crude extract and partition extract as well as better antioxidant activity in the flower fermented medium.
The fabrication of an optical biosensor by using stacked films where 3-methyl-2-benzothiazolinone hydrazone (MBTH) was immobilized in a hybrid nafion/sol-gelsilicate film and laccase in a chitosan film for the detection of phenolic compounds wasdescribed. Quinone and/or phenoxy radical product from the enzymatic oxidation ofphenolic compounds was allowed to couple with MBTH to form a colored azo-dye productfor spectrophometric detection. The biosensor demonstrated a linear response to catecholconcentration range of 0.5-8.0 mM with detection limit of 0.33 mM and response time of10 min. The reproducibility of the fabricated biosensor was good with RSD value of 5.3 %(n = 8) and stable for at least 2 months. The use of the hybrid materials of nafion/sol-gelsilicate to immobilize laccase has altered the selectivity of the enzyme to various phenoliccompounds such as catechol, guaicol, o-cresol and m-cresol when compared to the non-immobilized enzyme. When immobilized in this hybrid film, the biosensor response onlyto catechol and not other phenolic compounds investigated. Immobilization in this hybridmaterial has enable the biosensor to be more selective to catechol compared with the non-immobilized enzyme. This shows that by a careful selection of different immobilizationmatrices, the selectivity of an enzyme can be modified to yield a biosensor with goodselectivity towards certain targeted analytes.
Ultrasound-assisted extraction (UAE) was applied for the extraction of bioactive valuable compounds from winter melon (Benincasa hispida) seeds. Effects of amplitude (25-75%), temperature (40-60°C) and sonication time (20-60 min) on crude extraction yield (CEY) and radical scavenging activities (RSA, % inhibition of DPPH˙ and ABTS˙+ free radicals) of extracts were determined using complete randomised design (CRD). The results showed that the CEY and RSA of extracts significantly affected by independent variables. The maximum value of CEY (97.14±0.36 mgg-1), scavenging of DPPH˙ radicals (32.12 ± 0.38%) and scavenging of ABTS˙+ radicals (40.52±0.73%) were obtained at the combined treatment conditions of 75%, 55°C and 40 min. The UAE results obtained were compared with those achieved by using conventional Soxhlet extraction (CSE) method. It was found UAE allowed extraction at lower temperature and the extracts obtained posses higher quality compare with CSE. UAE is a promising environment friendly technique for the extraction of bioactive compounds from winter melon (Benincasa hispida) seeds.
This study investigated the effects of different percentages of ethanol (0 - 100%), extraction times (1 - 5 h) and temperatures (25 - 60°C) on total phenolic content (TPC) and antioxidant activity (AA) of sapodilla pulp and peel. TPC was determined by Folin-Ciocalteu reagent method, while AA was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, 2,2-azino-bis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay and β-carotene bleaching (BCB) assay. Based on the optimal extraction conditions used, sapodilla pulp extract had TPC of 3.89 mg GAE/g, 63.20% of DPPH scavenging activity, 4.30% of ABTS scavenging activity, 19.17% of BCB activity, and FRAP value of 15.24 mg TE/g; while its peel extract had TPC of 9.23 mg GAE/g, 92.95% of DPPH scavenging activity, 5.36% of ABTS scavenging activity, 8.14% of BCB activity, and 27.85 mg TE/g (FRAP value). Using the optimal extraction conditions for sapodilla pulp (40% ethanol as extraction solvent that extracted at 60°C for 4 h) and sapodilla peel (80% ethanol and 2 h extraction time at 40°C), highest antioxidants can be extracted from the pulp and peel.
The effects of ethanol concentration (0-100%, v/v), extraction time (60-300 min) and extraction temperature (25-65°C) on the extraction of phenolic antioxidants from Andrographis paniculata was evaluated using single-factor experiments. The following complementary assays were used to screen the antioxidant properties of the crude extracts: total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical-scavenging capacity and 2,2’-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity. The extraction conditions chosen had significant effects (p < 0.05) on the extraction of phenolic compounds and antioxidant capacity. The optimal conditions were 60% ethanol for 60 min at 65oC for phenolic compounds and at 25oC for antioxidant capacity. Strong negative significant (p < 0.05) correlations were observed between the phenolic compounds (TPC, TFC and CTC) and antioxidant capacity comprising ABTS (-0.924, -0.909, -0.887, respectively) and DPPH radical-scavenging capacities (-0.992, -0.938, -0.928, respectively) were determined under the influence of extraction temperature.
Papaya (Carica papaya L. cv. Hongkong) is an economically important fruit crop grown in Malaysia. During its ripening stages, (C. papaya L.) exhibits different physicochemical properties, antioxidant capacities, and sensory quality results. The objective of this study was to elucidate in detail the antioxidant capacity of C. papaya as determined by total phenol content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP),2,2-diphenyl-1-picrylhydrazyl (DPPH) and scavenging systemand (ABTS). The study also aimed to study physicochemical changes of papaya fruits based on measured pH, titratable acidity (TA), total soluble solids (TSS), moisture and fruit color at five different stages of ripening. The fruits were harvested at five different, stages RS1, RS2, RS3, RS4, and RS5 corresponding to 12, 14, 16, 18, and 20 weeks after anthesis, respectively. Significant differences were found at different stages of ripening. The pH of the fruit decreased significantly (P < 0.05), whereas TA, moisture, and TSS increased significantly (P < 0.05) during the ripening process. The redness (a*) and yellowness (b*) values of fruit color both increased significantly (P < 0.05), whereas
lightness (L*) varied. The total phenol content TPC, TFC, FRAP, DPPH and ABTS values increased significantly (P < 0.05) with the ripening process. Sensory evaluation based on the color, sweetness, sourness, flavor, and overall acceptance for the last three maturity stages was also performed. RS5 had a better score than RS3 or RS4. The results showed the important role of the ripening stage in increasing the antioxidant content of papaya fruits.
In a search for potent antileishmanial drug candidates, eighteen rhodacyanine analogues bearing fluorine or perfluoroalkyl substituents at various positions were synthesized. These compounds were tested for their inhibitory activities against Leishmania martiniquensis and L. orientalis. This 'fluorine-walk' analysis revealed that the introduction of fluorine atom at C-5, 6, 5', or 6' on the benzothiazole units led to significant enhancement of the activity, correlating with the less negative reduction potentials of the fluorinated analogues confirmed by the electrochemical study. On the other hand, CF3 and OCF3 groups were found to have detrimental effects, which agreed with the poor aqueous solubility predicted by the in silico ADMET analysis. In addition, some of the analogues including the difluorinated species showed exceptional potency against the promastigote and axenic amastigote stages (IC50 = 40-85 nM), with the activities surpassing both amphotericin B and miltefosine.
The presence of two different chromophores in benzothiazole molecule namely benzothiazole and aromatic rings lead to
interesting chemical and biological properties that attract more researches on the compounds. Three new benzothiazolylbenzoythiourea
compounds namely 1-(1,3-benzothiazol-2-yl)-3-(benzoylthiourea) (BBT), 1-(1,3-benzothiazol-2-yl)-3-
(4-chlorobenzoylthiourea) (BBT-4Cl) and 1-(1,3-benzothiazol-2-yl)-3-(4-methoxybenzoylthiourea) (BBT-4OCH3
different electron withdrawing substituents (R) at the para positions on the benzene ring of benzoylthiourea ring have
been synthesized from the reaction of R-benzoyl isothiocyanate (R= H, Cl, and OCH3
) and 2-aminobenzothiazole. The
compounds were characterized by spectroscopic techniques (infrared, 1
H proton NMR and UV-Vis). The IR spectra showed
the frequency signals of n (C=O), n (C=S), n (N-H) at 1664-1673, 1238-1249 and 3031-3055 cm-1, respectively. The 1
proton NMR spectra showed the presence of N-H amine and amide signals in the region of (12.14-12.35) and (14.17-14.43)
ppm, respectively. The proton signals of the two benzothiazole and benzoylthiourea moieties appear at 7.08-8.16 ppm.
A theoretical study based on Density Functional Theory (DFT) and Time-Dependent (TD) DFT was conducted to optimize
the geometrical structure and investigate the electronic properties of title compounds. The highest occupied molecular
orbital (HOMO) was found on the benzothiazole moiety; while, the lowest-unoccupied molecular orbital (LUMO) was
located at the benzoylthiourea fragment. The DFT optimized structures possessed an intramolecular hydrogen bonding
and the types of para substituents used influenced the properties of hydrogen bonding.
A new dihydrochalcone, 2',4'-dihydroxy-3,4-(2″,2″-dimethylchromeno)-3'-prenyldihydrochalcone (1) together with 4-hydroxyonchocarpin (2), isobavachalcone (3), 4',5-dihydroxy-6,7-(2,2-dimethylpyrano)-2'-methoxy-8-γ,γ-dimethylallyflavone (4), artocarpin (5) and cycloheterophyllin (6) were successfully isolated from the leaves and heartwoods of Artocarpus lowii King (Moraceae). The structures of these compounds were fully characterised using spectroscopic methods and by direct comparison with published data. These compounds were tested for their antioxidant and tyrosinase inhibitory activities. Compound (1) displayed moderate antioxidant activity towards DPPH and tyrosinase inhibitory activities with SC50 value of 223.8 μM and IC50 value of 722.5 μM, respectively. Among the isolated compounds, cycloheterophyllin (6) showed the most potential antioxidant activity with SC50 value of 320.0 and 102.8 μM for ABTS and DPPH radicals scavenging activities, respectively, and also exhibited highest FRAP equivalent value of 4.7 ± 0.09 mM. Compound (6) showed tyrosinase inhibitory activity with the IC50 value of 104.6 μM.
As a by-product of tropical fruit juice industry, passion fruit peel is a valuable functional food. It is rich in antioxidants. To determine its potential antioxidant properties of passion fruit peel, this study aimed to evaluate the effect of extraction conditions on total phenolic content and antioxidant activity.