Antimicrobial and Cytotoxic Activities of the Secondary Metabolites of Endophytic Fungi Isolated from the Medicinal Plant Hyssopus officinalis.

According to the World Health Organization, it is estimated that by 2050, drug-resistant infections could cause up to 10 million deaths annually. Therefore, finding a new generation of antibiotics is crucial. Natural compounds from endophytic fungi are considered a potential source of new-generation antibiotics. The antimicrobial and cytotoxic effects of ethyl acetate extracts of nine endophytic fungal isolates obtained from Hyssopus officinalis were investigated for bioassay-guided isolation of the natural compounds. An extract of isolate VII showed the highest antimicrobial activities against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus (30.12 ± 0.20 mm and 35.21 ± 0.20 mm) and Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa (30.41 ± 0.23 mm and 25.12 ± 0.25 mm) among the tested extracts of isolates. Molecular identification of isolate VII confirmed it as Chaetomium elatum based on sequencing of its ITS genes, and it was discovered that this was the first time C. elatum had been isolated from H. officinalis. This isolate was cultured at a large scale for the isolation and identification of the active compound. Penicillic acid was isolated for the first time from C. elatum and its chemical structure was established by NMR spectroscopy. The penicillic acid showed strong antibacterial activities against Bacillus subtilis and Staphylococcus aureus with 20.68 mm and 25.51 mm inhibition zones, respectively. In addition, MIC and MBC values and antibiofilm activities of penicillic acid were determined. It was found that penicillic acid reduced the level of biofilms in proportion to antibacterial activity.

New Triterpenoids from the Fruiting Bodies of Laetiporus sulphureus and Their Anti-Inflammatory Activity.

Laetiporus sulphureus is a popular medicinal mushroom with diverse pharmacological activities in many Asian countries. Four new triterpenoids, named sulphurenoids A-D (1-4), along with 12 known analogues, were isolated from the fruits of L. sulphureus. Nuclear magnetic resonance, infrared spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques were used for the investigation of the chemical structure of isolated compounds. In addition, the anti-inflammatory activity of three new compounds (2-4) was tested for NO production in lipopolysaccharide-induced RAW 264.7 cells. The IC50 values of isolated triterpenoids ranged from 14.3 to 42.3 µM, which were more effective than the positive control (IC50 for minocycline was 73.0 µM). The experimentally obtained anti-inflammatory activity data of L. sulphureus are in agreement with its traditional use.

Compositional Analysis and Potent Insecticidal Activity of Supercritical CO2 Fluid Extracts of Alcea nudiflora L. Leaves.

To mitigate potentially severe food shortages due to the exponential growth of the global population, it is of paramount importance to improve the yield and quality of globally harvested food crops. As pest control contributes to both these aspects, the development of safe and effective pesticides is one of the main strategies pursued in this direction in the context of agricultural chemistry. During our investigation of natural pesticides, a supercritical CO2 fluid extract of Alcea nudiflora L. was found to exert extremely potent insecticidal activity against aphids (Macrosiphum euphorbiae) and cowpea seed beetles (Callosobruchus maculatus) with LC50 values of 0.03 mg/mL (24 h exposure, contact method). The facts that their insecticidal activity is in the most potent class among the essential oils known to date, and that the extract did not show any toxicity toward beneficial insects such as ladybugs (Coccinella magnifica) and European honeybees (Apis mellifera Linnaeus), indicate that this extract could be a good, natural, and safe new pesticide candidate. A compositional analysis of this extract was carried out using GC/MS.

Secondary metabolites produced by endophytic Pantoea ananatis derived from roots of Baccharoides anthelmintica and their effect on melanin synthesis in murine B16 cells.

Five indole derivatives, 1H-indol-7-ol (1), tryptophol (2), 3-indolepropionic acid (3), tryptophan (4), 3,3-di(1H-indol-3-yl)propane-1,2-diol (5) and two diketopiperazines, cyclo(L-Pro-L-Tyr) (6), cyclo[L-(4-hydroxyprolinyl)-L-leucine (7) along with one dihydrocinnamic acid (8) were isolated from Pantoea ananatis VERA8, that endophytic bacteria derived from Baccharoides anthelmintica roots. This is a first report towards an isolation of endophytic strains (funji or bacteria) from the B. anthelmintica herb. The synergetic properties of the total extract compositions, as well as effects of the pure isolated secondary metabolites evaluated on their melanin synthesis in murine B16 cells towards for vitiligo treatment.

Isolation of cytotoxic sesquiterpene lactones from the Tanacetopsis karataviensis (Kovalevsk.) Kovalevsk.

The structures and anticancer effects of two sesquiterpene lactones, 1 R,10S,3S,4R-diepoxyguai-5S,6S,7S-11(13)-en-6,12-olide (1) and hanphyllin (2) isolated from the aerial part of Tanacetopsis karataviensis (Kovalevsk.) Kovalevsk were investigated. The compound 1 was isolated for the first time as a natural compound and its structure was investigated by HR-ESI-MS, IR and NMR techniques. The X-ray diffraction analysis was performed to accurately determine the spatial structures of 1 and 2. Furthermore, we evaluated the cytotoxic activity of 1 and 2, and the chloroform fraction which contains both of them. Cytotoxic activity revealed that the effect of the chloroform fraction is stronger in growth inhibition of HeLa (89.7%) and HEp-2 (63.0%) cancer cells than the effect of individual compounds 1 (55.9 and 36.3%), 2 (78.6 and 50.3%) and the reference cisplatin (58.0 and 46.8%) respectively. Moreover, the chloroform fraction is less toxic to the hepatocytes.

Phenolic glycosides from Nitraria sibirica leaves and their in vitro biological activities.

Seventeen phenolic glycosides were isolated from the Nitraria sibirica. Their structures were identified by the spectroscopic data and comparison with literatures as isovanillyl alcohol-7-O-ß-d-glucopyranoside (1), benzyl ß-primeveroside (2), benzyl-O-ß-d-glucopyranoside (3), 1-O-ß-d-glucopyranosyl-4-(8-hydroxyethyl)-2-methoxyphenyl (4), dehydrosyringin (5), trans-ferulic acid-4-O-ß-d-glucoside (6), cis-ferulic acid 4-O-ß-d-glucopyranoside (7), glucosyringic acid (8), 1-O-feruloyl-ß-d-glucoside (9), sachaloside VII (10), (3S, 5R, 6R, 7E, 9S)-megastigmane-7-ene-3-hydroxy-5,6-epoxy-9-O-ß-d-glucopyranoside(11), 3-hydroxy-4,5-dimethoxybenzyl alcohol (12), pinoresinol 4-O-ß-d-glucopyranoside (13), eucommin A (14), isoeucommin A (15), acanthoside (16), liriodendrin (17). All these compounds except compound 13 were isolated from the Nitraria genus for the first time. In bioactivity assays for all compounds, the compounds 8 and 15 were exhibited strong antioxidant activity (IC50 = 18.11 and 16.29 µM respectively), while compounds 3 and 11 were exhibited strong PTP1B enzymatic inhibition (IC50 = 6.97 and 11.76 µM, respectively). Furthermore, the compounds 10 and 17 were presented strong inhibitory capacities against Candida albicans (14.5 and 13.5 mm, respectively).

Two new glucoside derivatives of truxinic and cinnamic acids from Lavandula angustifolia mill.

A phytochemical investigations on the n-butanol fraction of Lavandula angustifolia Mill. residues resulted in the isolation of ten compounds, including two new ones, 4,4'dimethoxy-2,2'di-O-ß-d-glucopyranosyl-truxinate (1) and 2-(ß-d-glucosyloxy)-trans-cinnamic acid butyl ester (2), along with eight known compounds. The structures of compounds were confirmed by NMR and HR-ESI-MS techniques and comparison with published data. The NMR data for 3 were attributed for the first time. Compound 2 was proofed to be a natural compound in plant rather than a butyl ester artifact formed by esterification reaction with butanol by comparative HPLC-DAD analysis with the ethanol extract which was obtained prior to the application of butanol. All isolated compounds were evaluated for their antioxidant and anti-hypoglycaemic activities. Among them, compounds 4 and 5 showed strong anti-oxidant activities against DPPH with IC50 values of 12.99 and 31.74 µM, respectively. Compound 5 exhibited moderate inhibitory activity against PTP1B with an IC50 value of 31.28 µM.

The chemical components of Coreopsis tinctoria Nutt. and their antioxidant, antidiabetic and antibacterial activities.

Seventeen compounds were isolated from the capitula of Coreopsis tinctoria Nutt. with various column chromatographic methods and semi-preparative HPLC. Their structures were identified by the spectroscopic data and comparison with literatures as 2'-hydroxy-4,4'-dimethoxy-chalcone; (1), isoliquiritigenin (2), eriodictyol (3), naringenin (4), maritimetin (5), butin (6), taxifolin (7), luteolin (8), 7,3',4'-trihydroxyflavone (9), 8,3',4'-trihydroxyflavone-7-O-ß-d-glucoside (10), quercetin (11), quercetagitin-7-O-ß-d-glucoside (12), quercetin-7-O-ß-d-glucoside (13), 3,4-dihydroxybenzoic acid (14), caffeic acid (15), coreoside B (16), and myo-inositol (17). Compounds 1, 4, 9, 10 and 17 were isolated from C. tinctoria Nutt. for the first time. Compounds 7 and 12 possessed the highest antioxidant activity (IC50 = 64.37 and 32.86 µg/ml, respectively) among the tested compounds (IC50 value of positive control was 5.34 µg/ml). Compound 7 exhibited potent PTP1B enzymatic inhibition with an IC50 value of 7.73 µg/ml (IC50 value of positive control is 1.46 µg/ml). Furthermore, compound 5 showed strong antibacterial activity against the Gram-positive bacterium, S. aureus.

Structural characterization and antioxidant activities of a water soluble polysaccharide isolated from Glycyrrhiza glabra.

A water-soluble polysaccharide, named GPN, with molecular mass 38.7 kDa was isolated from Glycyrrhiza glabra with hot water extraction, ethanol precipitation, and purified by column chromatography. Monosaccharide composition analysis confirmed the presence of predominant glucose (98.03%) and trace amount of mannose, arabinose, and galactose. Methylation and GC-MS analysis revealed that the main glycosidic bonds in GPN comprised 1,4-linked Glcp, T-linked Glcp, 1,4,6-linked Glcp, and 1,6-linked Glcp. Based on these results and 1D/2D NMR spectroscopy, GPN has a linear backbone of 1,4-linked α-D-Glcp and 1,6-linked α-D-Glcp which substituted at C-4 of glucose. The side chain probably composed from 1,4-linked to main side α-D-Glcp and terminal 1-linked ß-D-Glcp to the C-3 of D residue. Congo red assay confirmed the existence of triple helix structure. Moreover, SEM and XRD analysis revealed that the GPN had irregular fibrous, filaments like surface; and both crystalline and amorphous structure. GPN also displayed favorable thermal stability. Moreover, G.glabra polysaccharide showed good antioxidant activity.

Component composition of the extracts and essential oils from the Alhagi canescens, growing in Uzbekistan and their antimicrobial activity.

The volatile compounds of hexane, benzene extracts and essential oils (EOs) isolated by steam- and hydrodistillation methods from aerial part of Alhagi canescens were studied by GC-MS analysis. Seventeen components were found in the hexane and benzene extracts, among them palmitic acid (25.2 and 22.1%), neophytadiene (7.3 and 22.3%), cis-chrysanthenyl acetate (11.0% in benzene), cis-geranyl acetate (7.8% in benzene) were major components. The first time fifty-six volatile compounds were identified in the EOs and camphor (5.9 and 27.8%), bicyclogermacrene (13.4 and 4.0%), α-copaene (6.1 and 2.6%), (-)-germacrene D (10.8 and 3.6%) and eucalyptol (3.7 and 8.1%) were the main components. The benzene, hexane extracts and EOs were screened for their antibacterial and antifungal activity. The benzene extract possess the highest antibacterial activity against Bacillus subtilis (12.12 ± 0.20) and Staphylococcus aureus (10.04 ± 0.10).

New coumarin from the roots of Prangos pabularia.

The new coumarin 1, yuganin A (7-methoxy-8-((1S,2S)-1,2,3-trihydroxy-3-methylbutyl)-2H-chromen-2-one) along with nine known coumarins, heraclenol 3'-O-ß-D-glucopyranoside (2), oxypeucedanin hydrate 3'-O-ß-D-glucopyranoside (3), heraclenol (4), oxypeucedanin hydrate (5), osthole (6), oxypeucedanin (7), heraclenin (8), isoimperatorin (9), imperatorin (10) and the disaccharide sucrose (11), have been isolated from the roots of Prangos pabularia, and the structures of these isolated compounds were elucidated by spectroscopic means, especially, UV, HR-ESIMS, and 1D and 2D NMR spectroscopy. Furthermore, the anti-melanogenic effect of yuganin A and its inhibitory effect on B16 cells were evaluated. Yuganin A may be useful in the treatment of hyperpigmentation and as a skin-whitening agent in the cosmetics industry.

Phenolic glycosides from Lavandual angustifolia.

Four new phenolic glycosides (1-4), together with 12 known ones (5-16), were isolated from the essential oil extraction waste of Lavandula angustifolia. Their structures were unequivocally determined by extensive spectroscopic analysis (1D and 2D NMR, HR-ESI-MS, UV, and optical rotation), chemical method, and comparison with data reported in the literature. The antioxidant activities of all compounds and new compounds' influence on melanin content in B16 melanoma cells were examined, which indicated that compounds 1, 8, 13 had a certain degree of DPPH free radical scavenging activities, while only compound 2 could increase the melanin content with a dose-dependent manner.

Evaluation of the Antidiabetic Activity and Chemical Composition of Geranium collinum Root Extracts-Computational and Experimental Investigations.

The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of G. collinum. The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC50 values of 0.10 µg/mL and 0.09 µg/mL for the enzymes protein-tyrosine phosphatase (1B PTP-1B) and α-glucosidase, respectively. Phytochemical investigations of the 50% aqueous-ethanolic extract of G. collinum, led to the isolation of ten pure compounds identified as 3,3',4,4'-tetra-O-methylellagic acid (1), 3,3'-di-O-methylellagic acid (2), quercetin (3), caffeic acid (4), (+)-catechin (5), (-)-epicatechin (6), (-)-epigallocatechin (7), gallic acid (8), ß-sitosterol-3-O-ß-d-glucopyranoside (9), and corilagin (10). Their structures were determined based on 1D and 2D NMR and mass spectrometric analyses. Three isolated compounds exhibited strong inhibitory activity against PTP-1B, with IC50 values below 0.9 µg/mL, more effective than the positive control (1.46 µg/mL). Molecular docking analysis suggests polyphenolic compounds such as corilagin, catechin and caffeic acid inhibit PTP-1B and ß-sitosterol-3-O-ß-d-gluco-pyranoside inhibits α-glucosidase. The experimental results suggest that the biological activity of G. collinum is related to its polyphenol contents. The results are also in agreement with computational investigations. Furthermore, the potent antidiabetic activity of the 50% aqueous-ethanolic extract from G. collinum shows promise for its future application in medicine. To the best of our knowledge, we hereby report, for the first time, the antidiabetic activity of G. collinum.

GC-MS and q-NMR based chemotaxonomic evaluation of two Leonurus species.

INTRODUCTION: The genus Leonurus L. (fam: Lamiaceae) is represented in Uzbekistan by two species, L. panzerioides Popov. and L. turkestanicus V. I. Krecz. & Kuprian, which are used to treat nervous disorders and also as sedative and hypotensive agents. OBJECTIVES: To establish the taxonomic status of Leonurus panzerioides and L. turkestanicus based on their chemical constituents analysed by GC-MS and q-NMR. MATERIALS AND METHODS: Quantitative (1) H-NMR (q-NMR) was used to identify and quantify known major components in the methanol extracts of these two species. Additionally, the chemical composition of the essential oils obtained from the aerial parts of these plants were analysed by GC-MS. RESULTS: The q-NMR analyses of Leonurus panzerioides and L. turkestanicus revealed the presence of 8-acetylharpagide, harpagide, leonurine and stachydrine as major components. Using the GC-MS method, overall 24 and 39 constituents were identified, respectively, from L. panzerioides and L. turkestanicus oils. The major constituents of the essential oil of L. panzerioides were eugenol (30.9%) and p-vinyl guaiacol (15.8%), whereas thymol (40.1%) and octen-3-ol (13.1%) were the principal compounds in the essential oil of L. turkestanicus. CONCLUSION: The major components in Leonurus panzerioides and L. turkestanicus as identified by the GC-MS and q-NMR analyses, were similar to those present in other Leonurus species and thus provided chemotaxonomic evidence for the placement of these species under the genus Leonurus. Copyright © 2016 John Wiley & Sons, Ltd.

Phytochemical Profiling and Evaluation of Pharmacological Activities of Hypericum scabrum L.

Phytochemical investigations of ethyl acetate-soluble part of the aerial part of Hypericum scabrum L. delivered eight pure phenolic compounds 1-8. The pure compounds were identified through physico-chemical, NMR (1D, 2D) and mass spectrometric studies as: 3-8''-bisapigenin (1), quercetin (2), quercetin-3-O-α-l-arabinofuranoside (3), quercetin-3-O-α-l-rhamnoside (4), quercetin-3-O-ß-d-glucopyranoside (5), quercetin-3-O-ß-d-galactopyranoside (6), (-)-epicatechin (7), (+)-catechin (8). Total polyphenolic compounds and total flavonoids contents were determined in the extract as 0.107 mg∙mg-1 and 0.023 mg∙mg-1 of the dried extract, respectively. Antioxidant activity using DPPH free radical scavenging assay delivered very strong activity for compounds 2 and 5, 6 and crude extract 10. Protein tyrosine phosphatase 1B (PTP-1B) inhibition experiment of isolated compounds and crude extracts resulted in significant inhibition activity for samples 2, 7a, 8a, 11 and 12 with IC50 values ranging from 1.57 to 2.91 µM. Antimicrobial activity of the pure compounds and extracts produced average results against Staphylococcus aureus, Escherichia coli and Candida albicans strains. From our literature survey, it appears that all pure compounds except 2 were isolated and reported for the first time in H. scabrum.

Discovery of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives as potent anticancer and antimicrobial agents and screening of anti-diabetic activity: synthesis and in vitro biological evaluation. Part 1.

Series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate (DDTD) derivatives: azomethines of DDTD (2a-l) have been synthesized and screened for their anticancer, antimicrobial and anti-diabetic activities. The novel synthesized compounds were characterized by (1)H, (13)C NMR, MS and FT-IR analyses. All compounds were evaluated for their antiproliferative activity against three types of cancer cell line such as T47D and MCF-7 (human breast cancer), Hela (human cervical cancer) and Ishikawa (human endometrial cancer) lines. The results showed that most compounds exhibited significant antiproliferative activity against breast cancer cells. The majority of azomethines DDTD influenced strongly against breast cancer cells T47D and MCF-7, among them compounds 2b (2.3 µM), 2c (12.1 µM), 2e (13.2 µM), 2i (14.9 µM), 2j (16.0 µM), 2k (7.1 µM), 2l (8.6 µM) manifest potent anticancer activity against cancer cell T47D than Doxorubicin (DOX, 15.5 µM). Compound 2j has shown potent activity on all three types of cancer cells concurrently and IC50 values were considerably low in comparison with positive control DOX. In addition, all compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538 (Gram positive bacteria), Escherichia coli ATCC 11229 (Gram negative bacteria) and Candida albicans ATCC 10231 (Fungi) strains and 2j which contains in the ring nitrofurfural fragment, showed the highest effect on the three species of microbial pathogens simultaneously. Some compounds induced enzymatic inhibition in a concentration-dependent manner on PTP-1B inhibitor.