Isolation, Identification, and Antimicrobial Evaluation of Secondary Metabolite from Serratia marcescens via an In Vivo Epicutaneous Infection Model.

Microbial secondary metabolites, which play a pivotal role in struggling with infectious diseases, are the new source for controlling bacterial contaminations and possess a strong antimicrobial potential. The present study is designed to evaluate the in vitro and in vivo bactericidal activities of prodigiosin against Staphylococcus aureus. For this purpose, Serratia marcescens was used to produce prodigiosin. Characterization of the prodigiosin was carried out using NMR. In addition, bioautographic detection of prodigiosin was detected by TLC. Antibacterial assays, in vivo epicutaneous infection tests, swap analyses, and histopathological examinations were determined. The results revealed that prodigiosin was detected by NMR and TLC. According to antimicrobial susceptibility tests, prodigiosin is an efficient bactericidal compound that demonstrated strong antibacterial activity toward S. aureus. In vivo, animal studies determined that the strong inhibition of S. aureus-caused epidermal infection occurs by prodigiosin at 48 h. Histopathological results showed that S. aureus + prodigiosin skin sections consist of improved and healthy tissues without any infection area compared with the S. aureus and control groups. The in vivo study verified the antibacterial results with swap analyses, and histopathological findings showed that prodigiosin is a promising microbial metabolite effective against S. aureus infection. This study proved that prodigiosin with excellent bioactivity exhibited antibacterial properties, which might possess massive potential for new therapeutic approaches using micro-organisms.

Design, semi-synthesis and examination of new gypsogenin derivatives against leukemia via Abl tyrosine kinase inhibition and apoptosis induction.

Chronic myelogenous leukemia (CML) is characterized by Philadelphia translocation arising from Bcr-Abl fusion gene, which encodes abnormal oncoprotein showing tyrosine kinase (TK) function. Certain mutations in kinase domain, off-target effects and resistance problems of current TK inhibitors require the discovery of novel Abl TK inhibitors. For this purpose, herein, we synthesized new gypsogenin derivatives (6a-l) and evaluated their anticancer effects towards CML cells along with healthy cell line and different leukemic cells. Among these compounds, compound 6l was found as the most active anti-leukemic agent against K562 CML cells compared to imatinib exerting less cytotoxicity towards PBMCs (healthy). This compound also revealed significant anti-leukemic effects against Jurkat cell line. Besides, compound 6l enhanced apoptosis in CML cells with 52.4 % when compared with imatinib (61.8 %) and inhibited Abl TK significantly with an IC50 value of 13.04 ± 2.48 µM in a large panel of kinases accentuating Abl TK-mediated apoptosis of compound 6l in CML cells. Molecular docking outcomes showed that compound 6l formed mainly crucial interactions in the ATP-binding cleft of Abl TK similar to that of imatinib. Ultimately, in silico pharmacokinetic evaluation of compound 6l indicated that this compound was endowed with anti-leukemic drug candidate features.

Triterpene glycosides from Silene odontopetala.

Silene species are known for their use in traditional medicine in treating several diseases. To the authors' knowledge there is no report on the chemical composition of S. odontopetala. Therefore, the phytochemical investigation of the methanol extract of S. odontopetala was carried out, leading to the isolation of six undescribed oleanane-type glycosides along with the known saponin azukisaponin IV. Their structures were elucidated by the analysis of 1D and 2D-NMR experiments, along with mass spectrometry analysis. The cytotoxic activity of oleanane-type saponins was evaluated against a small panel of cancer cell lines, including PC-3 (prostate carcinoma cells), MCF-7 (breast cancer cells), A549 (alveolar basal carcinoma cells), and HeLa (cervical carcinoma cells). Furthermore, the activity of isolated compounds against a normal cell line HEK-293, used for assessing their cytotoxicity, was evaluated.

Phytochemical investigation of Scabiosa sicula guided by a preliminary HPLC-ESIMSn profiling.

The genus Scabiosa (Caprifoliaceae) is represented by 80 species, widely used as medicinal plants for their positive effects on human diseases. On the basis of the interesting biological activity shown by Scabiosa spp., the phytochemical investigation of Scabiosa sicula L., never investigated before, was carried out. An initial LC-MS profile of the MeOH extract of S. sicula whole plant guided the isolation of 34 compounds, of which the structures were unambiguously elucidated by NMR analysis as phenolic compounds and triterpene saponins, among which eight undescribed compounds. Moreover, the total phenolic content of S. sicula methanol extract has been evaluated. On the basis of the pharmacological activities reported for Scabiosa species the antioxidant activity of the methanol extract was tested by TEAC and DPPH assays. Finally, the α-glucosidase inhibitory activity of the methanol extract was assayed, showing an IC50 value (49 µg/mL) comparable to that exerted by acarbose (90 µg/mL), used as positive control.

Radiolabeling and in vitro evaluation of a new 5-fluorouracil derivative with cell culture studies.

The clinical impact and accessibility of 99m Tc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5-Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5-Fluorouracil was synthesized as (1-[{1'-(1''-deoxy-2'',3'':4'',5''-di-O-isopropylidene-ß-D-fructopyranose-1''-yl)-1'H-1',2', 3'-triazol-4'-yl}methyl]-5-fluorouracil) (E) and radiolabeled with 99m Tc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell-binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF-5 cells. The radiochemical purity of the [99m Tc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF-7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 µM and 20.7 ± 2.77 µM for MCF-7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99m Tc has selective for breast cancer cells.

Chemical constituents of Silene montbretiana.

A new steroidal glycoside, 3- O-ß-d-glucopyranosyl-3ß,25-dihydroxy-5ß-cholest-7-en-6-one 25- O-ß-d-glucopyranoside (1), together with six known steroidal derivatives (2-7), one cerebroside (8) and one flavonoid (9) were isolated from Silene montbretiana Boiss (Caryophyllaceae), a perennial herb growing mainly in the Middle and East Anatolia, Azerbaijan, Iran, and Turkey. Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESI-MS analyses. The cytotoxicity against the cancer A549 (human alveolar basal carcinoma) and Hela (human epitheloid cervix carcinoma) cell lines has been evaluated. None of the tested compounds, in a range of concentrations between 12.5 and 100 µM, caused a significant reduction of the cell number.

Syntheses of 1,2,3-triazole-bridged pyranose sugars with purine and pyrimidine nucleobases and evaluation of their anticancer potential.

With the aim to create a library of compounds with potential bioactivities by combining special characteristics of two important groups such as nucleobases and carbohydrates, twenty 1,4-disubstituted-triazole nucleosides were synthesized in good yields (80-94%) using the copper catalyzed 'Click' reaction between azido-modified pento- or hexopyranoses and alkyne-bearing pyrimidine or purine nucleobases. Structural elucidation was made with the assistance of spectroscopic techniques such as FTIR, 1D-, 2D-NMR, and ESI-TOFMS. All the synthesized triazole nucleosides were evaluated for their cytotoxic activity against three human cancer cell lines (MDA-MB-231, Hep3B, PC-3) by using the MTT assay. Particularly, compounds 3a and 1b were identified as potential hits against Hep3B cell.

Synthesis, antimicrobial and cytotoxic activities, and structure-activity relationships of gypsogenin derivatives against human cancer cells.

A series of gypsogenin (1) derivatives (1a-i) was synthesized in good yields, and the derivatives' structures were established using UV, IR, (1)H NMR, (13)C NMR, and LCMS spectroscopic data. Among the tested compounds, 1a, 1b, 1d, 1e, and gypsogenin (1) showed antimicrobial activities against Bacillus subtilis and Bacillus thrungiensis, with inhibition zones of 10-14 mm. In addition, compounds 1b, 1d, and 1e showed antimicrobial activities against Bacillus cereus, with inhibition zones of 9-14 mm. Using six human cancer cell lines in vitro, the cytotoxic activities of all tested compounds were determined by calculating the IC50 values. Doxorubicin and paclitaxel were used as controls. Among the tested compounds, 1a, 1c, and 1d had inhibitory effects with IC50 values of 3.9 µM (HL-60 cells), 5.15 µM (MCF-7 cells), and 5.978 µM (HL-60), respectively. To determine the type of cell death, Hoechst 33258 (HO) and propidium iodide (PI) double staining was used. Especially, gypsogenin (1) and compound 1a triggered the apoptotic mechanism at a concentration of 20 µM. Thus, gypsogenin (1) and compounds 1a, 1c, and 1d possess varying degrees of biological activities and can be considered as potential antitumor agents.

Oleanane-type glycosides from Tremastelma palaestinum (L.) Janchen.

Three new oleanane-type glycosides, 1-3, were isolated from the whole plant of Tremastelma palaestinum (L.) Janchen, along with eight known triterpene glycosides. The structures of the new compounds were established as 3-O-[ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→3)-ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl]hederagenin (1), 3-O-[ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→3)-ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl]hederagenin 28-O-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl ester (2), and 3-O-[α-l-rhamnopyranosyl-(1→3)-ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl]oleanolic acid 28-O-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl ester (3) by using 1D- and 2D-NMR techniques and mass spectrometry. This is the first report on the phytochemical investigation of a species belonging to Tremastelma genus.

Oleanane glycosides from Astragalus tauricolus: isolation and structural elucidation based on a preliminary liquid chromatography-electrospray ionization tandem mass spectrometry profiling.

As a part of our ongoing research for bioactive compounds from Turkish Astragalus species, the investigation of Astragalus tauricolus has been carried out. An approach based on HPLC-ESIMS(n) experiments has been used to profile the triterpene glycosides occurring in the butanol extract of the whole plant. On the basis of the results of the online screening by HPLC-ESIMS(n), 22 oleanane-type triterpene glycosides, including ten compounds never reported before, were isolated, and their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analysis. Noteworthy, cycloartane-type triterpene glycosides, the main constituents of Astragalus spp., were not found. This peculiar feature characterizes a very limited group of Astragalus spp. The antiproliferative activity of the isolated compounds 1-12, 15, 17-19 was evaluated against a small panel of cancer cell lines. Only compound 11 showed an IC(50) of 22 µM against human leukemia cell line (U937). The other tested compounds, in a range of concentrations between 1 and 50 µM, did not cause any significant reduction of the cell number.

Triterpene glycosides from Astragalus angustifolius.

Six new cycloartane-type (1- 6) and four new oleanane-type (7- 10) triterpene glycosides were isolated from Astragalus angustifolius Lam., together with five known triterpene glycosides. Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analysis. Compounds 1- 3 are glycosides of cycloastragenol, while compounds 4- 6 show the C-24 epimer of cycloastragenol as aglycone, encountered for the first time in nature. All compounds were evaluated for their antiproliferative activity in Hela, H-446, HT-29, and U937 cell lines. Only compound 8 displayed a weak activity with IC (50) values of 36 and 50 µM against Hela and HT-29 cell lines, respectively.

Triterpene saponins from Cyclamen hederifolium.

Five triterpene saponins never reported before, hederifoliosides A-E, and four known triterpene saponins were isolated from the tubers of Cyclamen hederifolium. The structures of hederifoliosides A-E were determined as 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-oic acid 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-oic acid 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-al 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-[ß-D-glucopyranosyl-(1 → 6)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 30-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-3ß,16α,30-trihydroxyolean-12-en-28-al 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 30-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-3ß,16α,28,30-tetrahydroxyolean-12-en 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. The cytotoxic activity of the isolated compounds was evaluated against a small panel of cancer cell lines including Hela, H-446, HT-29, and U937. None of the tested compounds, in a range of concentrations between 1 and 50 µM, caused a significant reduction of the cell number.

Synthesis of egonol derivatives and their antimicrobial activities.

Eighteen derivatives of egonol (A-R) were synthesized and evaluated for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 6633, Candida albicans ATCC 10231 and Escherichia coli ATCC 8739 microorganisms comparing with egonol. The obtained data reported that compound B exhibited improved activities against all tested bacteria than egonol, others have shown different range of activities.

The Knoevenagel-Doebner reaction on 1,2-O-(2,2,2-trichloroethylidene) derivatives of D-gluco- and D-manno-furanose.

The synthesis of new α,ß-unsaturated furanuronic acid derivatives of α-gluco-, ß-gluco- and ß-manno-chloraloses via a convenient one pot procedure using the Knoevenagel-Doebner reaction approach are described. The dialdofuranose derivatives were reacted with malonic acid under Knoevenagel-Doebner reaction conditions and (E)-α,ß-unsaturated furanuronic acid derivatives were obtained.

Determination of some chemical parameters and antimicrobial activity of traditional food: mesir paste.

The antimicrobial activities and some chemical properties of the traditional Turkish food called mesir paste were studied. Results of chemical analysis for moisture and volatiles, water-insoluble components, refractive index, soluble solids content, raw fiber, invert sugar, total ash, 5-hydroxymethylfurfural, acidity, and pH were calculated as 17.06%, 2.55%, 1.491, 80.2%, 0.70%, 40.54%, 0.13%, 44 mg/kg, 0.9% anhydrous citric acid, and 3.6, respectively. Mesir paste was extracted individually by six solvents with different polarity, and antimicrobial activities of each extracts were determined against 12 microbial strains, mostly food-borne, including pathogens, by the agar well diffusion method. All extracts obtained showed antimicrobial activity ranging from 8 mm to 40 mm, and the butanolic extract displayed stronger antimicrobial activity against all tested microorganisms; Gram-positive strains were found to be more sensitive than Gram-negative strains. Antimicrobial potency of n-butanol extracts of mesir paste was determined in term of minimal inhibitory concentration and minimal bactericidal concentration for the sensitive microorganisms. In addition, some commercial antibiotics such as ampicillin, gentamicin, and nystatin were used as positive controls to determine the sensitivity of the strains.

Alpha-glucosidase inhibitory constituents of Linaria kurdica subsp. eriocalyx.

Three known iridoid glycosides, antirrhide (1), antirrhinoside (2), and 5-O-beta-allosylantirrhinoside (3), and two known flavone glycosides, linariin (4"'-O-acetylpectolinarin) (4) and linarin (acacetin-7-O-beta-D-rutinoside) (5) were isolated from Linaria kurdica Boiss & Hohen. subsp. eriocalyx. The structures of the isolated compounds were established from spectroscopic evidence. Compounds 1-3 showed high inhibitory potential against alpha-glucosidase.

Monoterpenoid glucoindole alkaloids and iridoids from Pterocephalus pinardii.

A new secondary metabolite, pterocephaline, along with the known cantleyoside, 7alpha-morroniside, 3beta,5alpha-tetrahydrodesoxycordifoline lactam, 5S-5-carboxyvincoside, sweroside, and loganin have been isolated from the aerial parts of P. pinardii (Dipsacaceae). Moreover, cantleyoside-methyl-hemiacetal and cantleyoside-dimethyl-acetal were obtained as seco-iridoid artifacts. The structures were elucidated by extensive spectroscopic methods including 1D-((1)H, (13)C and TOCSY) and 2D-NMR (DQF-COSY, HSQC and HMBC). Monoterpenoid glucoindole alkaloids were encountered for the first time in Dipsacaceae family.