A Comparative Analysis of Polysaccharides and Ethanolic Extracts from Two Egyptian Sweet Potato Cultivars, Abees and A 195: Chemical Characterization and Immunostimulant Activities.

Sweet potato (Ipomoea batatas (L.) Lam.) belongs to family Convolvulaceae. The plant is distributed worldwide and consumed, especially for its edible tubers. Many studies have proved that the plant has variable biological activities such as antidiabetic, anti-cancer, antihypertensive, antimicrobial, and immunostimulant activities. The roots of sweet potatoes are rich in valuable phytochemical constituents that vary according to the flesh color. Our investigation focused on the chemical profiling of two Egyptian sweet potato cultivars, Abees and A 195, using UPLC-QTOF and the analysis of their polysaccharide fractions by GC-MS. Furthermore, we assessed the immunostimulant properties of these extracts in immunosuppressed mice. The study revealed that sweet potato roots contain significant concentrations of phenolic acids, including caffeoylquinic, caffeic, caffeoyl-feruloyl quinic, and p-coumaric acids, as well as certain flavonoids, such as diosmin, diosmetin, and jaceosidin, and coumarins, such as scopoletin and umbelliferone. Moreover, polysaccharides prepared from both studied cultivars were analyzed using GC-MS. Further biological analysis demonstrated that all the tested extracts possessed immunostimulant properties by elevating the level of WBCs, IL-2, TNF, and IFN-γ in the immunosuppressed mice relative to the control group with the highest values in polysaccharide fractions of A195 (the ethanolic extract showed a higher effect on TNF and IFN-γ, while its polysaccharide fraction exhibited a promising effect on IL-2 and WBCs). In conclusion, the roots of the Egyptian sweet potato cultivars Abees and A 195 demonstrated significant immunostimulant activities, which warrants further investigation through clinical studies.

Identification of Antimicrobial Metabolites from the Egyptian Soil-Derived Amycolatopsis keratiniphila Revealed by Untargeted Metabolomics and Molecular Docking.

Actinomycetes are prolific producers of bioactive secondary metabolites. The prevalence of multidrug-resistant (MDR) pathogens has prompted us to search for potential natural antimicrobial agents. Herein, we report the isolation of rare actinobacteria from Egyptian soil. The strain was identified as Amycolatopsis keratiniphila DPA04 using 16S rRNA gene sequencing. Cultivation profiling, followed by chemical and antimicrobial evaluation of crude extracts, revealed the activity of DPA04 ISP-2 and M1 culture extracts against Gram-positive bacteria. Minimum inhibitory concentrations (MIC) values ranged from 19.5 to 39 µg/mL. Chemical analysis of the crude extracts using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) led to the identification of 45 metabolites of different chemical classes. In addition, ECO-0501 was identified in the cultures with significant antimicrobial activity. Multidrug resistance in Staphylococcus aureus is reported to be related to the multidrug efflux pump (MATE). ECO-0501 and its related metabolites were subjected to molecular docking studies against the MATE receptor as a proposed mechanism of action. ECO-0501 and its derivatives (AK_1 and N-demethyl ECO-0501) had better binding scores (-12.93, -12.24, and -11.92 kcal/mol) than the co-crystallized 4HY inhibitor (-8.99 kcal/mol) making them promising candidates as MATE inhibitors. Finally, our work established that natural products from this strain could be useful therapeutic tools for controlling infectious diseases.

Cholinesterase Inhibitors from an Endophytic Fungus Aspergillus niveus Fv-er401: Metabolomics, Isolation and Molecular Docking.

Alzheimer's disease poses a global health concern with unmet demand requiring creative approaches to discover new medications. In this study, we investigated the chemical composition and the anticholinesterase activity of Aspergillus niveus Fv-er401 isolated from Foeniculum vulgare (Apiaceae) roots. Fifty-eight metabolites were identified using UHPLC-MS/MS analysis of the crude extract. The fungal extract showed acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory effects with IC50 53.44 ± 1.57 and 48.46 ± 0.41 µg/mL, respectively. Two known metabolites were isolated, terrequinone A and citrinin, showing moderate AChE and BuChE inhibitory activity using the Ellman's method (IC50 = 11.10 ± 0.38 µg/mL and 5.06 ± 0.15 µg/mL, respectively for AChE, and IC50 15.63 ± 1.27 µg/mL and 8.02 ± 0.08 µg/mL, respectively for BuChE). As evidenced by molecular docking, the isolated compounds and other structurally related metabolites identified by molecular networking had the required structural features for AChE and BuChE inhibition. Where varioxiranol G (-9.76 and -10.36 kcal/mol), penicitrinol B (-9.50 and -8.02 kcal/mol), dicitrinol A (-8.53 and -7.98 kcal/mol) and asterriquinone CT5 (-8.02 and -8.25 kcal/mol) showed better binding scores as AChE and BuChE inhibitors than the co-crystallized inhibitor (between -7.89 and 7.82 kcal/mol) making them promising candidates for the development of new drugs to treat Alzheimer's.

Penicillactonin and preaustinoid C, lactone-containing metabolites from a hot spring sediment Penicillium sp.

Phytochemical investigation of Penicillium sp. RO-11 strain, collected from the sediments of a hydrothermal spring located in the southwestern area of Saudi Arabia, afforded, along with previously isolated compounds, the undescribed polyketides penicillactonin (1), penipyranicin D (4) and isopyrenulin B (5) and the undescribed meroterpenoid preaustinoid C (7). The structures of these compounds were elucidated based on data from mass spectrometry, 1D and 2D NMR, and comparison between experimental and calculated ECD spectra. Penicillactonin and preaustinoid C bring unprecedented structural features, for which a biosynthetic rationale is proposed, further extending the chemodiversity associated to Penicillium fungi. Preaustinoid C showed significant activity against LPS-induced NO production and selective effect on IL-2 and IFN-γ gene regulation in activated Jurkat cells.

Headspace solid-phase microextraction method for extracting volatile constituents from the different parts of Saudi Anethum graveolens L. and their antimicrobial activity.

Anethum graveolens L. is a famous aromatic herb that is widely used as a spice and has been applied in folk medicine to cure many diseases. The current work was carried out to compare the chemical composition and antimicrobial potency of essential oils obtained from the different parts of Saudi Arabia. graveolens. The oil constituents were extracted by headspace solid-phase microextraction and were quantified and qualitatively identified using GC/MS. As a result, essential oil isolated from A. graveolens seeds exhibited the highest antimicrobial activity compared to oils isolated from other parts, followed by flowers, leaves and stems. All tested A. graveolens essential oil samples exhibited stronger antifungal activities against Aspergillus parasiticus when compared to itraconazole. To the best of our knowledge, the current work is the first report comparing different parts of Saudi A. graveolens plant with respect to their essential oil chemical composition and antimicrobial potentials. The essential oil of A. graveolens seeds have the highest contents of carvone and limonene and show superior antimicrobial activities compared to other parts of the plant.

Phytochemical Analysis of Anvillea garcinii Leaves: Identification of Garcinamines F-H and Their Antiproliferative Activities.

Anvillea garcinii is a medicinal plant used in the Arab region for intestinal diseases, lung and liver diseases, digestive problems, and as an antidiabetic agent. Repeated chromatographic purifications of A. garcinii leaves led to the isolation of three undescribed guaiane sesquiterpene derivatives, named garcinamines F-H, characterized by the presence of an amino acid unit, along with five known sesquiterpene lactones (garcinamines B-E and 9ß-hydroxyparthenolide). The structures of the new compounds were established using spectroscopic (1D and 2D NMR) and spectrometric methods (ESIMS). Garcinamine H possesses a double bond at the Δ1,10 position, a structural feature rarely reported in guaianolide-type sesquiterpenes. The antiproliferative activity of the isolated sesquiterpenes was screened against three different cancer cell lines, and 9ß-hydroxyparthenolide and garcinamines C and D displayed significant effects against lung carcinoma (A549), colon carcinoma (LoVo), and breast carcinoma (MCF7) cell lines.

Antibacterial and Antifungal Sesquiterpenoids from Aerial Parts of Anvillea garcinii.

Two new sesquiterpenoids belonging to the guaiane, 4α,9α,10α-trihydroxyguaia-11(13)en-12,6α-olide (1), and germacrane, 9ß-hydroxyparthenolide-9-O-ß-D-glucopyranoside (2), classes have been isolated from the leaves of the Saudi medicinal plant Anvillea garcinii along with seven known compounds (3-9). The structures of the new metabolites were elucidated by spectroscopic analysis, including one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). The antimicrobial properties of 1-9 were screened against seven different pathogenic microbes, and compounds 1-3 showed a potent antifungal activity.

X-ray crystallographic and validated HPTLC analysis of the biomarker chromone glucoside (schumanniofioside A) isolated from Acalypha fruticosa growing in Saudi Arabia.

A chromone glucoside 2-methyl-5,7-dihydroxychromone 5-O-ß-D-glucopyranoside (schumanniofioside A, compound 1) was isolated from the methanol extract of Acalypha fruticosa. The structure of compound 1 was fully assigned based on nuclear magnetic resonance (NMR) (1H, 13C and 2D) spectra and electrospray ionization mass spectrum (ESI-MS) in addition to X-ray Crystallography. The molecules were packed in the crystal structure by eight intermolecular O-H⋯O and C-H⋯O interactions. The structure of compound 1 belongs to monoclinic, P21, a = 9.1989 (4) Å, b = 4.6651 (2) Å, c = 20.4042 (7) Å, ß = 97.862 (3)°, V = 867.31 (6) Å3, Z = 2, wRref(F2) = 0.101, T = 100 K. Thus, the bond angles, bond lengths and absolute structure of compound 1 were confirmed by its X-ray structure. A validated HPTLC method was developed for the quantitative analysis of compound 1 in chloroform and methanol extracts of A. fruticosa. It was found to furnish a compact and sharp band of compound 1 at Rf = 0.13 ± 0.005 using chloroform, methanol and glacial acetic acid [17:3:0.5 (v/v/v)] as mobile phase. The LOD and LOQ for compound 1 were found to be 17.86 and 54.13 ng/band, respectively. Compound 1 was found in both chloroform and methanol extracts of the plant (0.03% w/w and 0.31% w/w, respectively). The proposed HPTLC method can be used for the further analysis of schumanniofioside A in different plant extracts, herbal formulations and biological samples as well as in process quality control.

Chemical Composition and Antimicrobial Activities of Essential Oils of Some Coniferous Plants Cultivated in Egypt.

Family Cupressaceae is the largest coniferous plant family. Essential oils of many species belonging to family Cupressaceae are known to have several biological activities specially antimicrobial activity. The essential oils from aerial parts of Calocedrus decurrens Torr., Cupressus sempervirens stricta L. and Tetraclinis articulata (Vahl) Mast. were prepared by hydrodistillation. The chemical composition of the essential oils has been elucidated by gas chromatography-mass spectroscopy analysis. The prepared essential oils were examined against selected species of Gram-positive, Gram-negative bacteria and Candida species. Broth dilution methods were used to detect minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). Sixteen compounds were identified in the essential oils of both Calocedrus decurrens and Cupressus sempervirens L. and fifteen compounds were identified in the essential oil of Tetraclinis articulata. δ-3-Carene (43.10%), (+)-Cedrol (74.03%) and Camphor (21.23%) were the major constituents in the essential oils of Calocedrus decurrens, Cupressus sempervirens L. and Tetraclinis articulata, respectively. The essential oils showed strong antimicrobial activities against the selected microorganisms in concentration range 0.02 3- 3.03 µL/mL. This study could contribute to the chemotaxonomic characterization of family Cupressaceae. In addition, it proved that the essential oils under investigation possess potential antimicrobial properties.

Effect of precursors feeding and media manipulation on production of novel anticancer pro-drug camptothecin from endophytic fungus

We have established methodology for the isolation and characterization of a novel endophytic fungus from the inner bark of medicinal plant Nothapodytes foetida, which produced camptothecin in Sabouraud broth (SB) under shake flask conditions. Camptothecin and its related compounds are at present obtained by extraction from intact plants, but fungal endopytes may be an alternative source of production. In present study we have observed the effect of different nutrient combinations and precursors (tryptophan, tryptamine, geraniol, citral, mevalonic acid and leucine) on the accumulation of camptothecin by endophytic fungus Entrophospora infrequens. The precursors were fed either alone or in combinations (tryptophan and geraniol, tryptophan and citral, tryptophan and mevalonic acid, tryptophan and leucine). The highest camptothecin content was observed in the range of 503 ± 25µg/100g dry cell mass in Sabouraud medium. Camptothecin content in the medium was increased by 2.5 folds by the presence of tryptophan and leucine whereas the production with trytophan was also significantly different from other treatments. Furthermore, the effect of fungal camptothecin on the morphology of human cancer cell lines was also studied. The treated cells showed reduction in size, condensation of nucleus and the protoplasmic extensions were reduced. All these characteristics are found in apoptotic cells.

Effect of precursors feeding and media manipulation on production of novel anticancer pro-drug camptothecin from endophytic fungus.

We have established methodology for the isolation and characterization of a novel endophytic fungus from the inner bark of medicinal plant Nothapodytes foetida, which produced camptothecin in Sabouraud broth (SB) under shake flask conditions. Camptothecin and its related compounds are at present obtained by extraction from intact plants, but fungal endopytes may be an alternative source of production. In present study we have observed the effect of different nutrient combinations and precursors (tryptophan, tryptamine, geraniol, citral, mevalonic acid and leucine) on the accumulation of camptothecin by endophytic fungus Entrophospora infrequens. The precursors were fed either alone or in combinations (tryptophan and geraniol, tryptophan and citral, tryptophan and mevalonic acid, tryptophan and leucine). The highest camptothecin content was observed in the range of 503 ± 25µg/100g dry cell mass in Sabouraud medium. Camptothecin content in the medium was increased by 2.5 folds by the presence of tryptophan and leucine whereas the production with trytophan was also significantly different from other treatments. Furthermore, the effect of fungal camptothecin on the morphology of human cancer cell lines was also studied. The treated cells showed reduction in size, condensation of nucleus and the protoplasmic extensions were reduced. All these characteristics are found in apoptotic cells.

Discovering some novel tetrahydroquinoline derivatives bearing the biologically active sulfonamide moiety as a new class of antitumor agents.

The present article describes the synthesis of some novel 4-(2-amino-3-cyano-4-(substituted-aryl)-5-oxo-5,6,7,8-tetrahydroquinolin-1(4H)-yl)benzenesulfonamide (23-41) starting with 4-(3-oxo-cyclohex-1-enylamino)benzenesulfonamide (3). All the newly synthesized compounds were evaluated for their in vitro antitumor activity. Compounds 32, 25, 41, 35, 33, and 37 with IC50 values (2.5, 3, 5, 10, 12, and 12.5 microg/mL) are more potent and efficacious than Doxorubicin (CAS-23214-92-8) as reference drug with (IC50 value=37.5 microg/mL). Also, compounds 28, 30, 31, and 34 (with IC50 values=25 microg/mL) are nearly as active as Doxorubicin.

Novel quinolines and pyrimido[4,5-b]quinolines bearing biologically active sulfonamide moiety as a new class of antitumor agents.

Some novel quinolines and pyrimido[4,5-b]quinolines have been synthesized. The structures of which were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in-vitro antitumor activity against Ehrlich Ascites Carcinoma (EAC) cells. Compounds 24, 19 and 12 showed higher activity with IC(50) values (5.5, 6.9, 7 microg/ml) when compared with Doxorubicin as a reference drug (IC(50) value 38 microg/ml).

3-O-trans-caffeoylisomyricadiol: a new triterpenoid from Tamarix nilotica growing in Saudi Arabia.

A detailed chemical study of the aerial parts of Tamarix nilotica (Tamaricaceae) from Saudi Arabia led to the isolation of a new pentacyclic triterpenoid, 3-O-trans-caffeoylisomyricadiol, in addition to nine known compounds. The structures of all isolated compounds were unambiguously elucidated by 1D, 2D NMR, and mass spectrometry. In the radical scavenging (DPPH) assay, 3-O-trans-caffeoylisomyricadiol exhibited potent antioxidant activity with an IC50 value of 3.56 microM, while that for quercetin (standard antioxidant) was 5.72 microM.

Synthesis and biological evaluation of 2-amino-7,7-dimethyl 4-substituted-5-oxo-1-(3,4,5-trimethoxy)-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile derivatives as potential cytotoxic agents.

A large number of antimitotic drugs, derived from natural sources or chemically synthesized, have been identified and shown to interfere with the tubulin system. Inhibition of tubulin polymerization is among the important targets useful in the cancer therapy. The present work reports the synthesis of some novel quinoline derivatives bearing a trimethoxyphenyl moiety. The trimethoxybenzene moiety has been reported to be crucial to obtain relevant cytotoxic and antitubulin responses. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Several compounds showed interesting cytotoxic activities compared to the used reference drug.

Two new imidazole alkaloids from Leucetta chagosensis sponge.

Chemical investigation of the sponge Leucetta chagosensis, has led to the isolation of two new imidazole alkaloids, methyldorimidazole (1), preclathridine B (2) along with the known compounds naamine E (3) and leucettamine C (4). The structures of the newly compounds (1 and 2) were elucidated by employing spectroscopic techniques ((1)H NMR, MS and UV). The structures of the known compounds 3 and 4 were determined by comparison of their (1)H NMR and Mass spectroscopic data with published values.