ACE inhibitory,hypotensive and antioxidant peptide fractions from Mucuna pruriens proteins

Hydrolysates and peptide fractions obtained from Mucuna pruriens protein concentrate were studied for their angiotensin converting enzyme (ACE) inhibitory, hypotensive and antioxidant activities. The hydrolysate obtained by pepsin–pancreatin (HPP) was the most active with an ACE IC₅₀ value of 19.5 μg/mL, a Trolox equivalent antioxidant capacity (TEAC) value of 102.8 mM/mg and a ferric reducing power (FRP) IC₅₀ of 67.2 μg/mL. At a dose of 5 mg/kg HPP decrease systolic (32.2%) and diastolic (37%) blood pressure in rats more pronounced than Captopril. The peptide fraction <1 kDa from HPP was the most active with an ACE inhibitory of 10.2 μg/mL (IC₅₀), a TEAC value of 709.8 mM/mg and a FRP IC₅₀ of 54.9 μg/mL. These results indicate that the hydrolysates and peptide fractions of M. pruriens would be used as nutraceuticals ingredients for preventing and providing therapy against hypertension and diseases related to oxidative damage.     

Larvicidal activities of the stem bark extract and rotenoids of Millettia usaramensis subspecies usaramensis on Aedes aegypti L. (Diptera: Culicidae)

The dichloromethane/methanol (1:1) extract of the stem bark of Millettia usaramensis subspecies usaramensis was tested for its larvicidal activity against the 4th instar Aedes aegypti larvae and demonstrated activity with LC₅₀ value of 50.8 ± 0.06 μg/mL at 48 h. Compounds isolated from the extract were also tested for their larvicidal activities, and the rotenoid usararotenoid-A (LC₅₀ 4.3 ± 0.8 μg/mL at 48 h) was identified as the most active principle. This compound appears to be the first rotenoid having a trans-B/C ring junction and methylenedioxy group at C-2/C-3 with high larvicidal activity. Related rotenoids with the same configuration at the B/C-ring junction did not show significant activity at 100 μg/mL.     

Extreme effects of Seabuckthorn extracts on influenza viruses and human cancer cells and correlation between flavonol glycosides and biological activities of extracts

Seabuckthorn is a medicinal plant that is used to prevent cold. It was tested for its metabolic content followed by activity against cancer and virus. The metabolic distribution of different polarity solvent extractions from the leaves was analyzed by LC–MS/MS. Flavonol glycoside contents in EA and Bu extracts were higher than MeOH and DW was observed. MeOH and EA extracts recorded high activity against influenza A/PR virus with IC₅₀ of 7.2 μg/mL and 10.3 μg/mL compared with known drug Oseltamivir of 60.3 μg/mL. A similar trend showed in influenza A/Victoria virus. In case of influenza B viruses such as B/Lee and B/Maryland, EA extract (2.87 μg/mL and 4.5 μg/mL of IC₅₀) emerged strongest among other extracts and Oseltamivir (103.73 μg/mL and 71.6 μg/mL). Each extract showed potent anticancer activities. Interestingly, Bu extract showed stronger anticancer activity against human cancer cells such as NCL-H1299, HeLa, SKOV and Caski (8.2 μg/mL, 8.6 μg/mL, 18.2 μg/mL and 9.2 μg/mL of IC₅₀) respectively. Correlation study reveals that aglycones and flavonol mono-glycosides highly correlated with anti-influenza activities but not correlated with anticancer activities. Reversely, di-glycosides and tri-glycosides have a high correlation with cytotoxic effect with both normal and cancer cells. Therefore, this study provides significant information concerning Seabuckthorn for further medicinal drug development.     

Benzimidazole-based antibacterial agents against Francisella tularensis

Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC₉₀ values in the range of 0.35–48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2–3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.     

Simultaneous determination of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol in rat plasma by liquid chromatography–mass spectrometry: Application to pharmacokinetics

A rapid high-performance liquid chromatography–mass spectrometry (HPLC–MS) method was developed and validated for simultaneous quantification of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol in rat plasma after oral administration of ginger oleoresin. Plasma samples extracted with a liquid–liquid extraction procedure were separated on an Agilent Zorbax StableBond-C₁₈ column (4.6 mm × 50 mm, 1.8 μm) and detected by MS with electrospray ionization interface in positive selective ion monitoring (SIM) mode. Calibration curves (1/x² weighted) offered satisfactory linearity (r² > 0.995) in a wide linear range (0.0104–13.0 μg/mL for 6-gingerol, 0.00357–4.46 μg/mL for 8-gingerol, 0.00920–11.5 μg/mL for 10-gingerol and 0.00738–9.22 μg/mL for 6-shogaol). The lower limit of quantification (LLOQ) was in a range of 3.57–10.4 ng/mL. The analytes and internal standard can be baseline separated within 6 min. Inter- and intra-day assay variation was less than 15%. This developed method was successfully applied to pharmacokinetic studies of ginger oleoresin after oral administration to rats. Glucuronide of 6-gingerol was determined after β-glucuronidase hydrolysis for more information, and the intestinal glucuronidation was further confirmed by comparison of plasma samples of hepatic portal vein and femoral vein.     

Isolation,structure, and bioactivities of abiesadines A–Y, 25 new diterpenes from Abies georgei Orr

Twenty-five new (abiesadines A–Y, 1–25) and 29 known (26–54) diterpenes were isolated from the aerial parts of Abies georgei. Abiesadine A (1) is a novel 8,14-seco-abietane, while abiesadine B (2) is a novel 9,10-seco-abietane. The structures of the new compounds were established on the basis of spectroscopic data analysis. Manool (52) showed the strongest effect against LPS-induced NO production in RAW264.7 macrophages with the IC₅₀ value of 11.0 μg/mL. In another anti-inflammatory assay against TNFα-triggered NF-κB activity, (12R,13R)-8,12-epoxy-14-labden-13-ol (54) exhibited the strongest effect (IC₅₀ = 8.7 μg/mL). For antitumor assays, pomiferin A (26) and 8,11,13-abietatriene-7α,18-diol (29) both showed the most significant activity against LOVO cells (IC₅₀ = 9.2 μg/mL). While 7-oxocallitrisic acid (46) exhibited significant cytotoxicity against QGY-7703 tumor cells (IC₅₀ = 10.2 μg/mL).     

Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity

From the leaves of Nelumbo nucifera (an aquatic plant), one new compound, 24(R)-ethylcholest-6-ene-5α-ol-3-O-β-d-glucopyranoside (1), along with 11 known metabolites (2–12), were isolated and identified by spectroscopic methods including 1D- and 2D NMR. Antifungal activity for (R)-roemerine (3) (IC₅₀/MIC = 4.5/10 μg/mL against Candida albicans) and antimalarial activity for (R)-roemerine (3) and N-methylasimilobine (5) (IC₅₀ = 0.2 and 4.8 μg/mL for the D6 clone, respectively, and 0.4 and 4.8 μg/mL for the W2 clone, respectively) was observed. None of the compounds were cytotoxic to Vero cells up to a concentration of 23.8 μg/mL. NMR data for 10-eicosanol (7) and 7,11,15-trimethyl-2-hexadecanone (10) are presented for the first time. An analysis of the structure–activity relationship shows that the substituents in position C-1 and C-2 of aporphine alkaloids are crucial for the antimalarial activity.     

Antimicrobial and cytotoxic activities of the crude extracts of Dietes bicolor leaves,flowers and rhizomes

The crude extracts of Dietes bicolor leaves, flowers and rhizomes were subjected to comparative antimicrobial screening against two Gram-positive, two Gram-negative bacteria and four fungal strains using the agar well diffusion method. The minimum inhibitory concentrations (MIC) of the tested extracts were also determined. Furthermore, the cytotoxic activity was evaluated. D. bicolor extracts generally demonstrated notable broad spectrum antimicrobial activities (MIC values ≤ 500 μg/mL) against all tested pathogens. D. bicolor leaf extract showed potent broad spectrum antimicrobial activity with MIC values ranging between 0.24 and 31.25 μg/mL against all tested pathogens. Moreover, the flowers extract exhibited promising antimicrobial activities, displaying MIC values ranging between 1.95 and 125 μg/mL against the tested bacteria and fungi. However, the rhizomes extract showed moderate antimicrobial activity with MIC values ranging between 31.25 and 500 μg/mL. Despite the potent antimicrobial activity of D. bicolor extracts, they were ineffective as cytotoxic agents against nine tested cancer cell lines, displaying 50% inhibitory concentration (IC₅₀) values above 100 μg/mL. The reported potent antimicrobial activity along with the lack of measurable cytotoxic activity indicated that the antimicrobial activity of D. bicolor crude extracts is mediated through a mechanism other than cytotoxicity. These results suggest that D. bicolor can act as a potential source for natural antibacterial and antifungal agents with a good safety profile at a preliminary level.     

Two polymethoxylated flavonoids with antioxidant activities and a rearranged clerodane diterpenoid from the leaf exudates of Microglossa pyrifolia

Three novel compounds; two polymethoxylated flavonoids, 5,7,4′-trihydroxy-3,8,3′,5′-tetramethoxyflavone (1), 5,7,3′-trihydroxy-3,8,4′,5′-trimethoxyflavone (2), and a clerodane diterpenoid; 8-acetoxyisochiliolide lactone (3) were characterized from the leaf exudates of Microglossa pyrifolia. In addition, three known polymethoxylated flavonoids including; 5,7,4′-trihydroxy-3,8,3′-trimethoxyflavone (4), 5,3′4′-trihydroxy-3,7,8-trimethoxyflavone (5), 5,3′4′-trihydroxy-7-methoxyflavanone (6) and a clerodane diterpenoid; 7,8-epoxyisocholiolide lactone (7) were identified. Their structures were determined on the basis of spectroscopic evidence. All the compounds did not exhibit antiplasmodial and antimicrobial activities at 47.6 μg/mL and were not cytotoxic at 5 μg/mL. Compound 6 exhibited modest antileishmanial activity with IC₅₀ value of 13.13 μg/mL with 5 and 7 showing activities with IC₅₀ values of 31.13 and 38.00 μg/mL, respectively, therefore inactive. The flavonoids (quercetin derivatives, 4 and 5) showed similar antioxidant activities, using 2,2-diphenylpicrylhydrazyl (DPPH) assay, with IC₅₀ values of 6.2 ± 0.3 μg/mL for 4 (17.3 μM) and 5 (17.8 μM) respectively. These activities were comparable to that of the standard quercetin (IC₅₀ value of 6.0 ± 0.2 μg/mL (19.9 μM)), irrespective of methylation of the characteristic hydroxyl groups expected to be responsible for activity and additional substitution at C-8 in ring A of the flavonoid ring. These studies revealed that the presence of an hydroxyl group at C-4′ positions and oxygenation at C-3 in flavone skeleton, appears to be necessary for good antioxidant activities as encountered in compounds 1, 4 and 5. Substantial reduction in antioxidant activity was shown by methoxylation of the 4′-OH as observed in compound 2 with an IC₅₀ value of 8.79 ± 0.3 μg/mL (24.4 μM).     

New nemadectin congeners with acaricidal and nematocidal activity from Streptomyces microflavus neau3 Y-3

Two nemadectin congeners 1 and 2 were isolated from the fermentation broth of a mutant strain (Y-3) of Streptomyces microflavus neau3. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compound 2 possessed a 5-membered ring lactone that is unprecedented among known milbemycins and avermectins. Both compounds 1 and 2 exhibited potent acaricidal activity and nematocidal activity. Especially, compound 2 demonstrated impressive acaricidal activity against adult mites with an IC₅₀ of 2.3 ± 0.9 μg/mL and mite eggs with an IC₅₀ of 17.5 ± 2.1 μg/mL and nematocidal activity against Caenorhabditis elegans with an IC₅₀ of 0.7 ± 0.2 μg/mL, which are higher than those of nemadectin and the known commercial acaricide and nematocide milbemycin A3/A4.     

Optimization of ultrasound-assisted extraction conditions for total phenols with anti-hyperglycemic activity from Psidium guajava leaves

The high concentration of total phenolic compounds (TPC) in Psidium guajava leaf extracts (GvEx) is correlated to its anti-hyperglycemic activity. In this study, we established the optimum ultrasound extraction conditions for maximizing TPC yield. The response surface methodology (RSM) was employed for empirical model building. The maximum value of TPC (26.12%) was obtained at solvent to solid ratio (v/w) of 12.1, extraction temperature of 59.8 °C, and extraction time of 5.1 min. The anti-hyperglycemic activity of GvEx was compared to the commonly used diabetic drug acarbose. The IC₅₀ of GvEx for α-amylase and α-glucosidase inhibition was 50.5 μg/mL and 34.6 μg/mL, respectively. However, the IC₅₀ of acarbose for α-amylase and α-glucosidase inhibition was 95.3 μg/mL and 1075.2 μg/mL, respectively. In conclusion, GvEx obtained under optimum extraction conditions had higher anti-hyperglycemic activity than acarbose. In addition, the recommended extraction procedures for GvEx save time and are environmentally friendly.     

Antiviral activity of 2,3′-anhydro and related pyrimidine nucleosides against hepatitis B virus

Various 2,3′-anhydro analogs of 5-substituted 1-(2-deoxy-β-d-lyxofuranosyl)uracils (10–15) and a related 1-(3-O-mesyl-2-deoxy-β-d-lyxofuranosyl) pyrimidine nucleoside analog (18) have been synthesized for evaluation as a new class of potential anti-HBV agents. The compounds 10, 12, and 15 demonstrated most potent anti-HBV activities against duck HBV (DHBV) and human HBV with EC₅₀ values in the range of 2.5–10 and 5–10 μg/mL, respectively, at non-toxic concentrations (CC₅₀ = >200 μg/mL). The nucleoside 18 also demonstrated significant anti-HBV activity against DHBV with an EC₅₀ value of 2.5 μg/mL, however, it was less active against HBV in 2.2.15 cells (EC₅₀ = >10 μg/mL).     

Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B and PTP1B inhibitors

A series of novel thiadiazole amide derivatives have been synthesized and evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed inhibitory activities against Cdc25B (IC₅₀ = 1.18–8.01 μg/mL) and PTP1B (IC₅₀ = 0.85–8.75 μg/mL), respectively. Moreover, compounds 5b and 4l were most potent with IC₅₀ values of 1.18 and 0.85 μg/mL for Cdc25B and PTP1B, respectively, compared with reference drugs Na₃VO₄ (IC₅₀ = 0.93 μg/mL) and oleanolic acid (IC₅₀ = 0.85 μg/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments demonstrated that compound 5k was a specific inhibitor with the typical characteristics of a mixed inhibitor.     

New immunomodulatory steroidal alkaloids from Sarcococa saligna

Two new steroidal alkaloids, (20 S)-(bennzamido)-3β-(N,N-dimethyamino)-pregnane (1), and (20 S)-(bennzamido)-pregnane-3-one- (2), and two known steroidal alkaloids, pachysanaximine A (3) and 3β, 20α-diacetamido-5α-pregnane (4) were isolated from the whole plant of Sarcococca saligna. The structures of these compounds were identified with the help of spectroscopic techniques while spectra for known compounds were compared with spectra reported in literature. The immunomodulatory potential of the new compounds were found to be significant and dose dependent. Compound 1 showed inhibition of T cells proliferation at 10 μg/mL (95%), and inhibition of IL-2 production with an IC50 = 1.6 μg/mL.     

Identification of a bioactive compound isolated from Brazilian propolis type 6

A prenylated benzophenone, hyperibone A, was isolated from the hexane fraction of Brazilian propolis type 6. Its structure was determined by spectral analysis including 2D NMR. This compound exhibited cytotoxic activity against HeLa tumor cells (IC₅₀ = 0.1756 μM), strong antimicrobial activity (MIC range—0.73–6.6 μg/mL; MBC range—2.92–106 μg/mL) against Streptococcus mutans, Streptococcus sobrinus, Streptococcus oralis, Staphylococcus aureus, and Actinomyces naeslundii, and the results of its cytotoxic and antimicrobial activities were considered good.     

Constituents of Leonotis leonurus flowering tops

Phytochemical investigation of flowering tops of Leonotis leonurus, yielded a new diterpene ester, 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecan-1-yl-palmitate along with five known metabolites. The structures of all compounds were determined by spectroscopic methods including 1D- and 2D NMR spectroscopy. All the isolated compounds were evaluated for antimalarial, cytotoxicity and for antimicrobial activities. Antimalarial activity for luteolin 7-O-β-d-glucopyranoside (4) (IC₅₀ = 2.2 μg/mL for the D6 clone and 1.8 μg/mL for the W2 clone) was observed. Chloroquine and artemisinin were used as positive controls which showed IC₅₀ of 0.016 and 0.0048 μg/mL for the D6 clone, respectively, and IC₅₀ of 0.14 and 0.0047 μg/mL for the W2 clone, respectively. None of the compounds were cytotoxic to Vero cells up to a concentration of 4.76 μg/mL.     

Phytochemical composition and biological activities of Asteriscus graveolens (Forssk) extracts

In the present study the phytochemical composition and biological activities of the aerial part extracts of Asteriscus graveolens against pathogenic bacteria and leishmania parasite were evaluated. Phytochemical analysis revealed the presence of polyphenols, flavonoids and tannins. The ethyl acetate fraction exhibited high antioxidant potential of 359.72 ± 32.03 μg and 326.76 ± 15.86 μg of ascorbic acid equivalents and 13.32 ± 0.19 μg/mL by PM, FRAP and DPPH assays respectively. This fraction also displayed a moderate antibacterial activity against Listeria monocytogenes ATCC 19115 (MIC = 0.312 mg/mL) and strong antileishmanial activity against both promastigote and amastigote forms with IC50 ranging from 22.93 ± 0.39 μg/mL to 35.23 ± 0.62 μg/mL. Furthermore the ethyl acetate fraction exhibited low cytotoxicity and good selectivity index towards the macrophage cell line Raw 264.7. HPLC analysis of the active fraction revealed the presence of hydroxycinnamic acid as major compound (30.56%). Asteriscus graveolens is a promising source of bioactive compounds that could be potentially used in cosmetic and pharmaceutical industry.     

Green biosynthesis of silver nanoparticles from Annona squamosa leaf extract and its in vitro cytotoxic effect on MCF-7 cells

The biological method for the synthesis of silver nanoparticles (AgNPs) using Annona squamosa leaf extract and its cytotoxicity against MCF-7 cells are reported. The synthesized AgNPs using A. squamosa leaf extract was determined by UV–visible spectroscopy and it was further characterized by FT-IR, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Zeta potential and energy dispersive spectrometric (EDS) analysis. The UV–visible spectrum showed an absorption peak at 444 nm which reflects surface plasmon resonance (SPR) of AgNPs. TEM photography showed biosynthesized AgNPs were predominantly spherical in shape with an average size ranging from 20 to 100 nm. The Zeta potential value of ?37 mV revealed the stability of biosynthesized AgNPs. Furthermore, the green synthesized AgNPs exhibited a dose-dependent cytotoxicity against human breast cancer cell (MCF-7) and normal breast epithelial cells (HBL-100) and the inhibitory concentration (IC₅₀) were found to be 50 μg/mL, 30 μg/mL, and 80 μg/mL, 60 μg/ml for AgNPs against MCF-7 and normal HBL-100 cells at 24 h and 48 h incubation respectively. An induction of apoptosis was evidenced by (AO/EtBr) and DAPI staining. Application of such eco-friendly nanoparticles makes this method potentially exciting for the large scale synthesis of nanoparticles.     

Aspernolides F and G,new butyrolactones from the endophytic fungus Aspergillus terreus

Two new butyrolactones: aspernolides F (6) and G (7), together with three stigmasterol derivatives: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), and stigmasta-4,6,8(14), 22-tetraen-3-one (3), two meroterpenoids: terretonin A (4) and terretonin (5), and a butyrolactone derivative: butyrolactone VI (8) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were determined by spectroscopic means (1D, 2D NMR, and HRESIMS), as well as optical rotation measurement and comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. Compound 1 displayed a potent activity against MRSA and C. neoformans with IC₅₀ values of 0.96 μg/mL and 4.38 μg/mL, respectively compared to ciprofloxacin (IC₅₀ 0.07 μg/mL) and amphotericin B (IC₅₀ 0.34 μg/mL), respectively. While, 6 showed good activity against C. neoformans (IC₅₀ 5.19 μg/mL) and mild activity against MRSA (IC₅₀ 6.39 μg/mL). Moreover, 1 and 2 exhibited very good anti-leishmanial activity towards L. donovani with IC₅₀ values of 4.61 and 6.31 μg/mL, respectively and IC₉₀ values of 6.02 and 16.71 μg/mL, respectively.     

The synthesis and biological evaluation of some caffeic acid amide derivatives: E-2-Cyano-(3-substituted phenyl)acrylamides

A series of caffeic acid amide derivatives 2-cyano-(3-substituted phenyl)acrylamides were synthesized via Knoevenogal condensation of substituted benzaldehydes with cyanoacetamides. The structure of compound 1f was determined as E-isomer by X-ray diffractive analysis. The biological screening tests in vitro showed that compound 1b has obvious inhibitory activities against human gastric carcinoma cell line BGC-823, human nasopharyngeal carcinoma cell line KB and human hepatoma cell line BEL-7402 with IC₅₀ values of 5.6 μg/mL, 13.1 μg/mL and 12.5 μg/mL, respectively. Some preliminary structure–activity relationships (SAR) were also proposed which may provide a direction for further study.