Evaluation of in vitro free radical scavenging potential of Streptomyces sp. AM-S1 culture filtrate

The present study was carried out to determine the free radical scavenging potential of culture filtrate of Streptomyces sp. AM-S1. Antioxidant activity of culture filtrate, lyophilized culture filtrate and ethyl acetate extract of Streptomyces sp. AM-S1 was determined by various in vitro assays such as ferric reducing power assay, phosphomolybdenum reduction, DPPH and ABTS radical scavenging activities. The results revealed that the culture filtrate of Streptomyces sp. AM-S1 effectively scavenged DPPH (IC₅₀ 90.2 μl/ml) and ABTS (IC₅₀ 13.2 μl/ml) radicals in a concentration dependent manner. In all the assays, ethyl acetate extract registered higher antioxidant activity when compared with the lyophilized culture filtrate (LCF). In addition, ethyl acetate extract (1123.4 μmole Fe(II)/mg extract) exhibited higher ferric reducing activity than the standard BHA (814.4 μmole Fe(II)/mg extract). Further works are needed on the isolation and identification of antioxidant molecules from the ethyl acetate extract of Streptomyces sp. AM-S1 culture filtrate.     

Glutathione S-transferase pi (GST-pi) inhibition and anti-inflammation activity of the ethyl acetate extract of Streptomyces sp. strain MJM 8637

To investigate the anti-cancer properties of soil-borne actinobacteria, MJM 8637, the glutathione S-transferase pi (GST-pi) assay, anti-tumor necrosis factor (TNF)-α assay, the level of antioxidant potential by DPPH radical scavenging activity, NO scavenging activity, and ABTS radical scavenging activity in ethyl acetate extract were determined. The 16S rDNA sequencing analysis revealed that Streptomyces sp. strain MJM 8637, which was isolated from Hambak Mountain, Korea, has 99.5% similarity to Streptomyces atratus strain NBRC 3897. The physiological and the morphological characteristics of the strain MJM 8637 were also identified. The ethyl acetate extract of MJM 8637 inhibited TNF-α production approximately 61.8% at concentration 100 μg/ml. The IC₅₀ value of the strain MJM 8637 extract on GST-pi was identified to be 120.2 ± 1.6 μg/ml. In DPPH, NO, and ABTS radical scavenging assays, the IC₅₀ values of the strain MJM 8637 extract were found to be 977.2 μg/ml, 1143.7 μg/ml, and 454.4 μg/ml, respectively. The ethyl acetate extract of the strain MJM 8637 showed 97.2 ± 1.3% of cell viability at 100 μg/ml in RAW 264.7 cell viability assay. The results obtained from this study suggest that the ethyl acetate extract of Streptomyces sp. strain MJM 8637 could be considered as a potential source of drug for the cancers that have multidrug resistance with its GST-pi inhibition and anti-inflammation activities, and low cytotoxicity.     

Sex-specific reliability and multidimensional stability of responses to tests assessing neuromuscular function

The objective of this study was to estimate sex-specific effects in the test–retest cross-reliability of peripheral and central changes in nonlinear and linear measures of a surface electromyography signal during a brief (5 second) and sustained (2 minute) isometric maximal voluntary contraction, combined with superimposed electrical stimulation involving the ankle plantar flexors over five identical trials. In this study, we repeated the testing protocol used in our previous study of 10 women (age 20.9, SD = 0.3 years) (Bernecke et al., 2015) in a group of 10 men (age 21.2, SD = 0.4 years). Despite the central (sex effect; p < 0.05, η_p² > 0.71, SP > 70%) and peripheral fatigability (sex effect; p < 0.01, η_p² > 0.8, SP > 90%) during sustained isometric maximal voluntary contraction, and lower reliability for central activation ratio during brief (intraclass correlation coefficient [ICC] = 0.95 for men and ICC = 0.82 for women) and sustained maximal voluntary contraction (ICC > 0.82 for men and ICC > 0.66 for women) over ankle plantar flexors expressed in women more than in men, all the ICCs of all indices measured by tests assessing neuromuscular function across the five identical test–retest trials were found as meaningful (correlation significance of p < 0.05 was reached) and no significant differences were found between trials for any of the measured variables. In conclusion, the present study demonstrated greater central and peripheral fatigue for female participants following sustained (2 minute) isometric maximal voluntary contraction of the plantar flexor muscles for all repeated trials and indicated an acceptable agreement between measurements of the characteristic variables made using the three different devices (dynamometry, electrical stimulation, and surface electromyography) over time for both sexes.     

Evaluation of antioxidant and anticancer activities of chemical constituents of the Saururus chinensis root extracts

Evaluation of antioxidant and anticancer activities were screened by various Saururus chinensis root extracts. Four solvents (ethyl acetate, methanol, ethanol, and water) extracts were investigated for their total flavonoids, phenol contents and their antioxidant activity of DPPH (2,2-diphenyl-1-picrylhydrazyl), NO (nitric oxide), H₂O₂ (hydrogen peroxide), ABTS 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonicacid)diammonium assays, FRAP (ferric reducing ability of plasma) assays and anticancer activity. The total phenolic and flavonoid content of extracts were determined by using FC (Folin–Ciocalteu) and AlCl₃ colorimetric assay method. Total flavonoid content in these plants ranged from 24.7 to 72.1 mg g^?1 and amount of free phenolic compounds was between 11.2 and 67.1 mg g^?1 extract. The all extracts have significant levels of phenolics and flavonoids content. Anticancer activity was screened for MCF-7 breast cancer cell line. Ethanol extract shows significant of antioxidant activity and water extract shows significant of anticancer activity compared with standard (BHT) butylated hydroxy toluene. These ethanol and water extracts could be considered as a natural source for using antioxidant, and anticancer agents compared to commercial available synthetic drugs.     

Biological activities of plant extracts from Ficus elastica and Selaginella vogelli: An antimalarial,antitrypanosomal and cytotoxity evaluation

The cytotoxic, antiplasmodial, and antitrypanosomal activities of two medicinal plants traditionally used in Cameroon were evaluated. Wood of Ficus elastica Roxb. ex Hornem. aerial roots (Moraceae) and Selaginella vogelii Spring (Selaginellaceae) leaves were collected from two different sites in Cameroon. In vitro cell-growth inhibition activities were assessed on methanol extract of plant materials against Plasmodium falciparum strain 3D7 and Trypanosoma brucei brucei, as well as against HeLa human cervical carcinoma cells. Criteria for activity were an IC₅₀ value < 10 μg/mL. The extract of S. vogelii did not significantly reduce the viability of P. falciparum at a concentration of 25 μg/mL but dramatically affected the trypanosome growth with an IC₅₀ of 2.4 μg/mL. In contrast, at the same concentration, the extract of F. elastica exhibited plasmodiacidal activity (IC₅₀ value of 9.5 μg/mL) and trypanocidal (IC₅₀ value of 0.9 μg/mL) activity. Both extracts presented low cytotoxic effects on HeLa cancer cell line. These results indicate that the selected medicinal plants could be further investigated for identifying compounds that may be responsible for the observed activities and that may represent new leads in parasitical drug discovery.     

The assessment of anti-tumoral activity of polysaccharide extracted from terrestrial filamentous fungus

Fungal polysaccharides are well-known for the medicinal properties such as antitumor and immunomodulating effects. Hence, this study evaluated antitumor effects of polysaccharide extracted from Fusarium sp. isolated from soil samples of Karaj district, Alborz, Iran along with its taxonomic study. The filamentous fungus strain FK1 was isolated from the soil sample of Karaj, Iran. The strain was identified based on cultural, morphological and 18 S rRNA gene parameters as Fusarium. Further, the strain Fusarium was cultured in fermented broth of modified (PDB) for 10  days at 25 °C. The polysaccharide of strain FK1 was extracted from the mycelium free supernatant by boiling water method and evaluated for antitoxicity effect on two human cancer cell lines: HeLa cell line and Lymphoblastoid cell line (LCL) by MTT method. Findings revealed that water-extracted from mycelia polysaccharide of strain FK1 had the highest cytotoxicity effect against LCL which is the cause of B lymphocyte cancer, at 50  μg/ml concentration dose (114 ± 1.63) followed by 100  μg/ml (105 ± 0.57) and 10  μg/ml (104 ± 0.57), while it did not have a considerable effect on HeLa cell line. Fusarium could be alternative sources as an antitumor component.     

Antioxidative,antimicrobial and cytotoxic effects of the phenolics of Leea indica leaf extract

This study investigated the phytochemical, antioxidative, antimicrobial and cytotoxic effects of Leea indica leaf ethanol extract. Phytochemical values namely total phenolic and flavonoid contents, total antioxidant capacity, DPPH radical scavenging effect, FeCl₃ reducing power, DMSO superoxide scavenging effect and Iron chelating effects were studied by established methods. Antibacterial, antifungal and cytotoxic effects were screened by disk diffusion technique, food poison technique and brine shrimp bioassay, respectively. Results showed the total phenolic content 24.00 ± 0.81 g GAE/100 g, total flavonoid content 194.68 ± 2.43 g quercetin/100 g and total antioxidant capacity 106.61 ± 1.84 g AA/100 g dry extract. Significant (P < 0.05) IC₅₀ values compared to respective standards were recorded in DPPH radical scavenging (139.83 ± 1.40 μg/ml), FeCl₃ reduction (16.48 ± 0.64 μg/ml), DMSO superoxide scavenging (676.08 ± 5.80 μg/ml) and Iron chelating (519.33 ± 16.96 μg/ml) methods. In antibacterial screening, the extract showed significant (P < 0.05) zone of inhibitions compared to positive controls Ampicillin and Tetracycline against Gram positive Bacillus subtilis, Bacillus cereus, Bacillus megaterium, and Staphylococcus aureus and Gram negative Salmonella typhi, Salmonella paratyphi, Pseudomonas aeroginosa, Shigella dysenteriae, Vibrio cholerae, and Escherichia coli. Significant minimum inhibitory concentrations compared to tetracycline were obtained against the above organisms. In antifungal assay, the extract inhibited the growth of Aspergillus flavus, Candida albicans and Fusarium equisetii by 38.09 ± 0.59, 22.58 ± 2.22, and 22.58 ± 2.22%, respectively. The extract showed a significant LC₅₀ value compared to vincristine sulfate in cytotoxic assay. The results evidenced the potential antioxidative, antimicrobial and cytotoxic capacities of Leea inidica leaf extract to be processed for pharmaceutical use.     

Antioxidant, α-amylase inhibitory and oxidative DNA damage protective property of Boerhaavia diffusa (Linn.) root

Boerhaavia diffusa Linn. of family Nyctaginaceae is a known traditional medicinal plant and has been used in the treatment of many free radical mediated diseases. Excessive formation of free radicals, either reactive oxygen species (ROS) or reactive nitrogen species (RNS) is responsible for damaging various biomolecules like DNA, lipids and proteins. The present investigation was initially carried out to explore the possible link between antioxidant, oxidative DNA damage protective and α-amylase inhibitory property of B. diffusa root extract and their bioactive fraction. Our results illustrated an enhanced DPPH radical scavenging activity/antioxidant power of methanol root extract (IC₅₀ < 250 μg/ml) than ethanol (IC₅₀ = 250 μg/ml) and aqueous extract (IC₅₀ > 250 μg/ml). In addition, the methanol root extract also showed better oxidative DNA damage protective activity and α-amylase inhibitory property than ethanol and aqueous root extract. Phytochemical screening of B. diffusa ethanol and methanol root extract showed the presence of saponins, alkaloids, flavonoids, glycosides and terpenoids in large amount. By means of repetitive preparatory TLC and HPLC the potent antioxidant and α-amylase inhibitory fraction was isolated from methanol root extract. Our results illustrated that DPPH radical scavenging activity (IC₅₀ < 250 μg/ml) and oxidative DNA damage protective and α-amylase inhibitory activity of the isolated/purified bioactive compound from methanol extract were significantly closer to that of crude extract, which in turn confirm that antioxidant and antidiabetic property of methanol root extract resides in this fraction and established a significant correlation between antioxidant and inhibitory α-amylase property of this bioactive fraction compound. These profound effects of B. diffusa methanol root extract and its purified fraction against oxidative plasmid DNA damage, antioxidant and α-amylase inhibitory activity may explain its extensive use in daily life and possible health benefits.     

Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects

A new Mannich base series of piperazine linked berberine analogues was furnished in this study to screen the antioxidant and anticancer potential of the resultant analogues. Alkoxy group at a C-9 position of berberine was converted to hydroxyl functionality to enhance the ability of final scaffolds binding to the target of drug action mainly through hydrophobic effect, conjugation effect, whereas Mannich base functionality was introduced on the C-12 position of berberine. Scaffolds were investigated for their free radical scavenging antioxidant potential in FRAP and DPPH assay, whereas tested to check their Fe⁺³ reducing power in ABTS assay. The radical scavenging potential of the final derivatives 4a–j was found excellent with IC₅₀s, <13 μg/mL and < 8 μg/mL in DPPH and ABTS assay, respectively, whereas some analogues showed significant Fe⁺³ reducing power with absorption at around 2 nm in the FRAP assay. Anticancer effects of titled compounds were inspected against cervical cancer cell line Hela and Caski adapting SRB assay, in which analogues 4a–j presented <6 μg/mL of IC₅₀s, and >30 of therapeutic indices, thus exerting low cytotoxic values against Malin–Darby canine kidney (MDCK) cell lines at CC₅₀s >125 μg/mL. Hence, from the bioassay outcomes it can be stated that these analogues are dual active agents as the scavengers of reactive oxygen species and inhibitors of the cancerous cells as compounds with halogen functional group have overall good pharmacological potential in assays studied in this research. Correct structure of the final compounds was adequately confirmed on the basis of FT-IR and ¹H NMR as well as elemental analyses.     

Middle Jurassic Ginkgo leaves from the Daohugou area,Inner Mongolia,China and their implication for palaeo-CO2 reconstruction

Well-preserved Ginkgo leaves with cuticle were collected from the Middle Jurassic Jiulongshan Formation in the Daohugou area, Inner Mongolia, China, which form the common elements in the Daohugou flora. Three new species of Ginkgo are recognized and their leaf morphology and cuticular structure are described for the first time. Two different pCO₂ proxy models were applied to reconstruct palaeo-atmospheric CO₂ concentration by using these new Ginkgo material. NLE (nearest living equivalent) suggests a semi-quantitative pCO₂ estimate as 839 ± 99 ppmv with Carboniferous standardization and 419 ± 49 ppmv with Recent standardization. While Barclay’s revised SI-pCO₂ regression suggests the estimates as 405 ± 71 ppmv. The results show that the pCO₂ estimate is higher than today’s atmospheric CO₂ concentration but lower than most of the other results on the Jurassic Period. Combined with the floristic composition, the climate at 165 Ma in the Daohugou area is inferred to be warm temperate.     

Beneficial effects of a medicinal herb,Cirsium japonicum var. maackii,extract and its major component,cirsimaritin on breast cancer metastasis in MDA-MB-231 breast cancer cells

The biological activities of the ethanol extract from Cirsium japonicum var. maackii (ICF-1) and its major component, polyphenol cirsimaritin, were investigated as part of the search for possible alternative drugs for breast cancer. Three in vitro cell-based assays were used: the cell proliferation assay, tube-formation assay, and Western blot analysis. Both the ICF-1 extract and cirsimaritin inhibited the viability of HUVECs in a dose-dependent manner. The inhibition achieved was 36.89% at a level of 200 μg/ml by the ICF-1 extract and 62.04% at a level of 100 μM by cirsimaritin. The ICF-1 extract and cirsimaritin reduced tube formation by 12.69% at level of 25 μg/ml and 32.18% at the levels of 6.25 μM, respectively. Cirsimaritin inhibited angiogenesis by downregulation of VEGF, p-Akt and p-ERK in MDA-MB-231 cells, suggesting that cirsimaritin is potentially useful as an anti-metastatic agent. The present study demonstrated that Cirsium japonicum extract and its active component cirsimaritin is an excellent candidate as an alternative anti-breast cancer drug.     

Antibacterial activity of selected medicinal plants of northwest Pakistan traditionally used against mastitis in livestock

The present study aimed to investigate the efficacy of traditionally used anti-mastitis plants (Allium sativum, Bunium persicum, Oryza sativa and Triticum aestivum) in northwest Pakistan against bacterial pathogens. Selected plants were phytochemically screened for Alkaloids, Flavonoids, and Saponins and checked for in vitro antibacterial activity at concentration of 50 mg/ml against S. aureus, E. coli and K. pneumoniae by agar well diffusion method. Minimum inhibitory concentration and minimum bactericidal concentration was determined against multidrug resistant bacteria using tube dilution method. All extracts were found to significantly inhibit (p < 0.01, p < 0.05) the activity against bacterial strains examined. Among phytochemicals, alkaloids of all tested antimastitis plants produced significantly higher inhibition zones against bacteria. The minimum inhibitory concentration and minimum bactericidal concentration of phytochemicals and crude methanolic extracts against tested bacterial strains ranged between 12.5–50 mg/ml and 25–50 mg/ml, respectively. Medicinal plants traditionally used against mastitis are therapeutically active against bacterial pathogens. A. sativum and B. persicum were found to be potential candidate species for the development of novel veterinary drugs with low cost and fewer side effects.     

Discovery of (R)-5-(benzo[d][1,3]dioxol-5-yl)-7-((1-(vinylsulfonyl)pyrrolidin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (B6) as a potent Bmx inhibitor for the treatment of NSCLC

Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer. Owing to its high CLogP (4.07) and low aqueous solubility (<0.01 mg/ml), resulting in unfavorable bioavailability, ibrutinib requires high dosages to achieve good clinical response in the treatment of non-small cell lung cancer (NSCLC). In our effort to improve the CLogP of ibrutinib by structural optimization led to the discovery of a potent anti-cancer agent B6, with beneficial physicochemical parameters (CLogP = 2.56, solubility in water ≈ 0.1 mg/ml) meeting the principles of oral drugs. B6 exhibited anti-proliferation activities against EGFR-expressing cells, especially the mutant ones, such as H1975 (L858R/T790M, IC₅₀ = 0.92 ± 0.19 μM) and HCC827 (Del119 IC₅₀ = 0.014 ± 0.01 μM). Moreover, B6 significantly slowed down H1975 tumor growth with anti-tumor rate of 73.9% (p < 0.01). Enzyme potencies assay demonstrated B6 moderately selectively inhibited Bmx (IC₅₀ = 35.7 ± 0.1 nM) over other kinases. So, as a potent Bmx inhibitor, B6 has the potential to be an efficacious treatment for NSCLC with acquired drug resistance.     

Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies

The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC₅₀: 0.68 ± 0.13 μM) with strong DPPH and ABTS radical scavenging activity (IC₅₀: 13.77 ± 0.25 μM and IC₅₀: 12.59 ± 0.21 μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC₅₀: 0.74 ± 0.09 μM) and with DPPH and ABTS radical scavenging activity (IC₅₀: 13.52 ± 0.62 μM and IC₅₀: 13.13 ± 0.85 μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.     

Endothelium-dependent vasorelaxation in rat thoracic aorta by Mansoa hirsuta D.C.

The vasodilator effect of the ethanolic extract of Mansoa hirsuta leaves (EEF) was assayed in rat aortic rings. EEF produced a concentration-dependent vasodilatation (pIC₅₀=5.1±0.2), which was absent in endothelium-denuded vessels. The vasodilator effect of EEF was similar to a standardized ethanolic extract of Hancornia speciosa Gomes (pIC₅₀=5.1±0.1). The endothelium-dependent vasodilatation induced by EEF was abolished by L-NAME (100 μM), a nitric oxide (NO) synthase inhibitor, but not by indomethacin (10 μM; pIC₅₀=4.9±0.2), a cyclooxygenase inhibitor. The concentration–response curve of EEF was not modified by the addition of superoxide dismutase (SOD; 300 U/ml). In addition, EEF (50 μg/ml) displaced the 3-morpholino-sidnonimine (SIN-1; p<0.05) concentration–effect curve to the left, as well as SOD (300 U/ml). These findings lead us to conclude that EEF induces a NO- and endothelium-dependent vasodilatation in rat aortic preparations, and that this effect is, at least in some extent, due to an increase in the NO bioavailability as consequence of its antioxidant activity. The HPLC-DAD profile recorded for EEF indicates the presence of four major peaks with close retention times, exhibiting similar UV spectra with wavelength maxima compatible with heterogeneous proanthocyanidins.     

Isolation and purification of salvianolic acid A and salvianolic acid B from Salvia miltiorrhiza by high-speed counter-current chromatography and comparison of their antioxidant activity

Water-soluble salvianolic acid A (Sal A) and salvianolic acid B (Sal B) were successfully isolated and purified from the crude extract of Salvia miltiorrhiza by high-speed counter-current chromatography (HSCCC). The solvent system was n-hexane–ethyl acetate–methanol–water (3:6:6:10, v/v/v/v). 4.27 mg of Sal A and 32.09 mg of Sal B were obtained from 260 mg of the crude sample. The purities of Sal A and Sal B were 96.67% and 97.43%, respectively. Their structures were identified by ¹H NMR and ¹³C NMR. Antioxidant activities of Sal A and Sal B were also evaluated and compared by the methods of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS⁺) radical cation decolourisation assay. Both Sal A and Sal B showed high radical scavenging activities with their EC₅₀ values being 1.43 ± 0.09 and 1.81 ± 0.01 μg/ml in DPPH radical method. The ABTS results showed that Sal A and Sal B exhibited high total antioxidant activities, their EC₅₀ values were 1.35 ± 0.00 and 1.43 ± 0.01 μg/ml, respectively.     

Antileishmanial evaluation of clubbed bis(indolyl)-pyridine derivatives: One-pot synthesis,in vitro biological evaluations and in silico ADME prediction

A new series of bis(indolyl)-pyridine derivatives 6(a–m) were synthesized by Chichibabin reaction process and evaluated for antileishmanial and antibacterial activities to establish structure–activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, and ammonium acetate in the presence of camphor-10-sulfonic acid as a catalyst. The compounds 6d (IC₅₀ = 102.47 μM) and 6f (IC₅₀ = 99.49 μM) had shown promising antileishmanial against L. donovani promastigotes when compared with standard sodium stibogluconate (IC₅₀ = 490.00 μM). All the synthesized compounds (MIC range = 41.35–228.69 μg/mL) had shown potent antibacterial activity than standard ampicillin (MIC range = 100.00–250.00 μg/mL) against all the tested bacterial strains. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antileishmanial and antibacterial drug discovery initiatives.     

Anti-diabetic xanthones from the bark of Garcinia xanthochymus

An ethyl acetate extract the bark of Garcinia xanthochymus exhibited strong inhibition towards α-glucosidase and PTP1B with IC₅₀ values of 0.3 ± 0.1 μg/mL and 2.3 ± 0.4 μg/mL, respectively. Chemical constituents of the extract were therefore examined, and two new compounds, xanthochymusxanthones A (1) and B (2), along with ten known xanthones (3–12), were isolated. Their structures were determined using spectroscopic methods, mainly 1D and 2D NMR. Inhibitory activity of the isolated compounds was then tested, and subelliptenone F (12) showed significant effect towards α-glucosidase with IC₅₀ value of 4.1 ± 0.3 μM (compared with acarbose, IC₅₀ = 900.0 ± 3.0 μM) whilst xanthochymusxanthone B (2) exhibited remarkable activity towards PTP1B with IC₅₀ value of 8.0 ± 0.6 μM (compared with RK682, IC₅₀ = 4.4 ± 0.3 μM).     

Design and synthesis of new triazoles linked to xanthotoxin for potent and highly selective anti-gastric cancer agents

Two series of xanthotoxin-triazole derivatives were designed, synthesized, and studied for their antiproliferative properties. The in vitro cytotoxicity of the compounds in the AGS cancer cell line and the L02 normal cell line was evaluated via MTT assay. Among the synthesized compounds, 9-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-7H-furo[3,2-g]chromen-7-one (6p) was found to have the greatest antiproliferative activity against AGS cells (IC₅₀ = 7.5 μM) and showed better activity than the lead compound (xanthotoxin, IC₅₀ > 100 μM) and the reference drug (5-fluorouracil, IC₅₀ = 29.6 μM) did. The IC₅₀ value of 6p in L02 cells was 13.3 times higher than that in the AGS cells. Therefore, the compound exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil. Cell cycle analysis revealed that compound 6p inhibited cell growth via the induction of S/G2 phase arrest in AGS cells. Compound 6p was identified as a promising lead compound for the further development and identification of 1,2,3-triazole-based anticancer agents.     

Isolation of antioxidant constituents from Combretum apiculatum subsp. apiculatum

Species of the family Combretaceae are used extensively in traditional medicine against inflammation and infections, and although antibacterial activity has been reported in non-polar extracts, further rationale for the widespread use of the Combretaceae is expected to exist. Methanol extracts of leaves of ten different Combretum species were evaluated for antioxidant activity by spraying TLC chromatograms of each leaf extract with 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds with antioxidant activity were detected by bleaching of the purple DPPH colour. Leaf extracts of Combretum apiculatum subsp. apiculatum had the most antioxidant compounds. This species was consequently selected for phytochemical investigation. A DPPH assay-directed fractionation of the leaf extracts of C. apiculatum led to the isolation of four antioxidant compounds from the ethyl acetate and butanol soluble fractions. The structures of the compounds were determined by spectroscopic analyses (¹H-NMR, ¹³C-NMR and MS) and identified as: cardamonin (1), pinocembrin (2), quercetrin (3) and kaempferol (4). In a quantitative antioxidant assay, the more polar fractions (ethyl acetate and butanol) obtained by solvent–solvent fractionation had the highest antioxidant activity among the solvent fractions obtained from C. apiculatum, with EC₅₀ values of 3.91 ± 0.02 and 2.44 ± 0.02 μg/ml respectively. Of the four isolated compounds, quercetrin (4) and kaempferol (3) had the strongest antioxidant activity, with EC₅₀ values of 11.81 ± 85 and 47.36 ± 0.03 μM respectively. Cardamonin (1) and pinocembrin (2) did not demonstrate strong activity. L-ascorbic acid was used as standard antioxidant agent (EC₅₀ = 13.37 ± 0.20 μM or 2.35 μg/ml). The cytotoxicity of cardamonin and pinocembrin was evaluated on Vero kidney cells using the MTT (3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide) assay with berberine as positive control. At concentrations higher than 50 μg/ml of cardamonin or pinocembrin, the cells were not viable. Cardamonin was more toxic (LC₅₀ = 1.97 μg/ml) than pinocembrin (LC₅₀ = 29.47 μg/ml) and even the positive control, berberine (LC₅₀ = 12.35 μg/ml).