Feature-Based Molecular Networking for the Exploration of the Metabolome Diversity of Common Egyptian Centaurea Species in Relation to Their Cytotoxic Activity.

Centaurea is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian Centaurea species, C. lipii was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of C. lipii and compare it to other members of the genus in pursuance of identifying its bioactive principles. An LC-MS/MS analysis approach synchronized with feature-based molecular networks was adopted to offer a holistic overview of the metabolome diversity of the Egyptian Centaurea species. The studied plants included C. alexandrina, C. calcitrapa, C. eryngioides, C. glomerata, C. lipii, C. pallescens, C. pumilio, and C. scoparia. Their constitutive metabolome showed diverse chemical classes such as cinnamic acids, sesquiterpene lactones, flavonoids, and lignans. Linking the recorded metabolome to the previously reported cytotoxicity identified sesquiterpene lactones as the major contributors to this activity. To confirm our findings, bioassay-guided fractionation of C. lipii was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC50 of 1.817 µM against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of C. lipii and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.

Terpenoid bio-transformations and applications via cell/organ cultures: a systematic review.

Structurally diverse natural products are valued for their targeted biological activity. The challenge of working with such metabolites is their low natural abundance and complex structure, often with multiple stereocenters, precludes large-scale or unsophisticated chemical synthesis. Since select plants contain the enzymatic machinery necessary to produce specialized compounds, tissue cultures can be used to achieve key transformations for large-scale chemical and/or pharmaceutical applications. In this context, plant tissue-culture bio-transformations have demonstrated great promise in the preparation of pharmaceutical products. This review describes the capacity of cultured plant cells to transform terpenoid natural products and the specific application of such transformations over the past three decades (1988-2019).

Euphosantianane A⁻D: Antiproliferative Premyrsinane Diterpenoids from the Endemic Egyptian Plant Euphorbia Sanctae-Catharinae.

Euphorbia species are rich in diterpenes. A solvent extraction of Euphorbia sanctae-catharinae, a species indigenous to the Southern Sinai of Egypt, afforded several premyrsinane diterpenoids (1⁻4) as well as previously reported metabolites (5⁻13) that included three flavonoids. Isolated compounds were chemically characterized by spectroscopic analysis. Identified compounds were bioassayed for anti-proliferative activity in vitro against colon (Caco-2) and lung (A549) tumor cell lines. Compound 9 exhibited robust anti-proliferative activity against A549 cells (IC50 = 3.3 µM). Absolute configurations for 8 versus 9 were determined by experimental and TDDFT-calculated electronic circular dichorism (ECD) spectra.

Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition and In Silico Ligand Docking.

Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site.

Plant cell cultures: An enzymatic tool for polyphenolic and flavonoid transformations.

BACKGROUND: In the pharmaceutical sector, tissue culture techniques for large-scale production of natural chemicals can be a less expensive alternative to large-scale synthesis. Although recent biotransformation research have used plant cell cultures to target a wide range of bioactive compounds, more compiled information and synopses are needed to better understand metabolic pathways and improve biotransformation efficiencies. PURPOSE: This report reviews the biochemical transformation of phenolic natural products by plant cell cultures in order to identify potential novel biotechnological approaches for ensuring more homogeneous and stable phenolic production year-round under controlled environmental conditions. METHODS: Articles on the use of plant cell culture for polyphenolic and flavonoid transformations (1988 - 2021) were retrieved from SciFinder, PubMed, Scopus, and Web of Science through electronic and manual search in English. Following that, the authors chose the required papers based on the criteria they defined. The following keywords were used for the online search: biotransformation, Plant cell cultures, flavonoids, phenolics, and pharmaceutical products. RESULTS: The initial search found a total of 96 articles. However, only 70 of them were selected as they met the inclusion criteria defined by the authors. The analysis of these studies revealed that plant tissue culture is applicable for the large-scale production of plant secondary metabolites including the phenolics, which have high therapeutic value. CONCLUSION: Plant tissue cultures could be employed as an efficient technique for producing secondary metabolites including phenolics. Phenolics possess a wide range of therapeutic benefits, as anti-oxidant, anti-cancer, and anti-inflammatory properties. Callus culture, suspension cultures, transformation, and other procedures have been used to improve the synthesis of phenolics. Their production on a large scale is now achievable. More breakthroughs will lead to newer insights and, without a doubt, to a new era of phenolics-based pharmacological agents for the treatment of a variety of infectious and degenerative disorders.

New antimicrobial metabolites from the medicinal herb Artemisia herba-Alba.

Artemisia herba-alba is widely used in traditional medicines for the treatment of several diseases. From the aerial parts organic extract of A. herba-alba, two new compounds, 1,3,8-trihydroxyeudesm-4-en-7α,11ßH-12,6α-olide (1) and 5-ß-​D-​glucopyranosyloxy​-​7-methoxy-​6H-​benzopyran-​2-​one (2), respectively, together with five known metabolites: 3α,8ß-dihydroxygermacr-4(15),9(10)-dien-7ß,11αH,12,6α-olide (3), 1ß,8α-dihydroxy-11α,13-dihydrobalchanin (4), 11-epiartapshin (5), tomenin (6) and benzoic acid, p-​(ß-​D-​glucopyranosyloxy)​-​methyl ester (7), were isolated and identified. The chemical structures were proven depending upon spectroscopic analysis, including 1 D/2D NMR as and ESI-MS. Compound 1 inhibited Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. Compounds 2 and 3 exhibited antibacterial activity against both gram-positive and gram-negative bacteria.

Comparative Study on the Essential Oils from Five Wild Egyptian Centaurea Species: Effective Extraction Techniques, Antimicrobial Activity and In-Silico Analyses.

The genus Centaurea is recognized in folk medicine for anti-inflammatory, anti-itch, antitussive, purgative, astringent, and tonic activities. To study the chemical determinant for antimicrobial activity essential oils (EOs), five Centaurea species were analyzed including: C. scoparia, C. calcitrapa, C. glomerata, C. lipii and C. alexandrina. Conventional hydro-distillation (HD) and microwave-assisted extraction (MAE), as new green technologies, were compared for the extraction of essential oils. GC/MS analysis identified 120 EOs including mostly terpenoid except from C. lipii and C. alexandrina in which nonterpenoids were the major constituents. Major terpenoids included spathulenol, caryophyllene oxide and alloaromadendrene oxide-2. To probe antibacterial activity, potential EO inhibitors of a bacterial type II DNA topoisomerase, DNA gyrase B were screened via an in silico molecular docking approach. Spathulenol and alloaromadendrene oxide-2 possessed the best binding affinity in the ATP- binding pocket of Gyrase B enzyme. Principal component analysis and agglomerative hierarchical clustering were used for sample classification and revealed that sesquiterpenes contributed the most for accessions classification. In vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli and Aspergillus niger for all EOs were also evaluated. EOs from C. lipii, C. glomerata and C. calcitrapa exhibited significant MIC against S. aureus with an MIC value of 31.25 µg/mL.

Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells.

BACKGROUND: The multidrug resistance (MDR) phenotype encounters a major challenge to the success of established chemotherapy in cancer patients. We hypothesized that cytotoxic medicinal plants with novel phytochemicals can overcome MDR and kill MDR-cells with similar efficacy as drug sensitive cells. PURPOSE: We evaluated plant extracts from an unexplored ecosystem in Egypt with unusual climate and nutrient conditions for their activity against sensitive and multidrug-resistant cancer cell lines. MATERIAL AND METHODS/STUDY DESIGN: Methylene chloride: methanol (1:1) and methanol: H2O (7:3) extracts of 40 plants were prepared resulting in a sum of 76 fraction containing compounds with varying polarity. The resazurin reduction assay was employed to evaluate the cytotoxicity of these extracts on five matched pairs of drug-sensitive and their drug-resistant cell lines. Flow cytometry and Western blotting was used to determine cell cycle analyses, apoptosis, and autophagy. Reactive oxygen species (ROS) were measured spectrophotometrically. RESULTS: Extracts derived from Withania obtusifolia (WO), Jasonia candicans (JC), Centaurea lippii (CL), and Pulicaria undulata (PU) were the most active ones among 76 extracts from 40 Egyptian medicinal plants. They showed a significant reduction of cell viability on drug-sensitive CCRF-CEM leukemia cell line with IC50 values less than 7 µg/ml. Low cross-resistance degrees were observed in multidrug-resistant CEM/ADR5000 cells towards CL (1.82-fold) and JC (6.09-fold). All other drug-resistant cell lines did not reveal cross-resistance to the four extracts. Further mechanistic assessment have been studied for these four extracts. CONCLUSION: The methylene chloride: methanol (1:1) fractions of WO, JC, CL, and PU are promising cytotoxic extracts that could be used to combat MDR cancer cells through different cell death pathways.

Potency of extracts from selected Egyptian plants as inducers of the Nrf2-dependent chemopreventive enzyme NQO1.

Medicinal plants from the Egyptian Sinai Peninsula are widely used in traditional Bedouin medicine to treat a range of conditions including cancer, and as such are a promising resource for novel anti-cancer compounds. To achieve scientific justification of traditional use and/or to recommend the use of those plants as medicinal herbs for cancer chemoprevention, a group of 11 Sinai plants of different species that belong to 3 families (Asteraceae, Lamiaceae, and Euphorbiaceae) were biologically screened for cancer preventive activity using the chemoprevention marker enzyme NAD(P)H: quinone oxidoreductase 1 (NQO1). Among the fractions assayed, a solvent extract from Pulicaria incisa had potent NQO1 inducing activity. Further analysis of the mechanism of induction revealed the concentration-dependent stabilization of the transcription factor NF-E2 p45-related factor 2 (Nrf2) and a coordinate upregulation of the Nrf2-dependent enzymes NQO1, heme oxygenase 1 and glutathione S-transferase-Pi. These results establish P. incisa as a promising target for future phytochemical characterization for cancer preventive components.

A new steroid from the Red Sea soft coral Lobophytum lobophytum.

Chemical investigation of the soft coral Lobophytum lobophytum collected from the Red Sea led to the isolation of a new compound gorgostan-5,25-dien-3ß-ol (1), and two known compounds gorgosterol (2), and alismol (3). Structures were elucidated by employing extensive NMR and HR-ESI-MS experiments.

Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review.

Natural products are structurally and biologically interesting metabolites, but they have been isolated in minute amounts. The syntheses of such natural products help in obtaining them in bulk amounts. The recognition of microbial biotransformation as important manufacturing tool has increased in chemical and pharmaceutical industries. In recent years, microbial transformation is increasing significantly from limited interest into highly active area in green chemistry including preparation of pharmaceutical products. This is the first review published on the usage of microbial biocatalysts for some natural product classes and natural product drugs.

Evaluation of the essential oil of Foeniculum vulgare Mill (fennel) fruits extracted by three different extraction methods by GC/MS.

BACKGROUND: Hydrodistillation (HD) and steam-distillation, or solvent extraction methods of essential oils have some disadvantages like thermal decomposition of extracts, its contamination with solvent or solvent residues and the pollution of residual vegetal material with solvent which can be also an environmental problem. Thus, new green techniques, such as supercritical fluid extraction and microwave assisted techniques, are potential solutions to overcome these disadvantages. MATERIALS AND METHODS: The aim of this study was to evaluate the essential oil of Foeniculum vulgare subsp. Piperitum fruits extracted by three different extraction methods viz. Supercritical fluid extraction (SFE) using CO2, microwave-assisted extraction (MAE) and hydro-distillation (HD) using gas chromatography-mass spectrometry (GC/MS). RESULTS: The results revealed that both MAE and SFE enhanced the extraction efficiency of the interested components. MAE gave the highest yield of oil as well as higher percentage of Fenchone (28%), whereas SFE gave the highest percentage of anethol (72%). CONCLUSION: Microwave-assisted extraction (MAE) and supercritical fluid extraction (SFE) not only enhanced the essential oil extraction but also saved time, reduced the solvents use and produced, ecologically, green technologies.

Isolation and characterization of antineoplastic alkaloids from Catharanthus roseus L. Don. cultivated in Egypt.

Vinblastine and vincristine (the antileukemic agents) were isolated, in a pure form, from Catharanthus roseus L. Don., cultivated in Egypt, by several chromatographic techniques. Five modified methods for the preparation of total alkaloids were carried out. All the isolated mixtures were evaluated by HPLC and HPTLC analyses. The antineoplastic alkaloids; vinblastine and vincristine, were isolated by the use of vacuum liquid chromatographic column on silica gel : aluminium oxide (1:1) mixed bed vacuum liquid chromatography (VLC), Charcoal column, and finally purified by centrifugally accelerated radial chromatography (Chromatotrone).

Chemical Investigation of Some Capparis Species Growing in Egypt and their Antioxidant Activity.

Capparis cartilaginea and C. deserti growing in Egypt were investigated for their glucosiolates and rutin content. From Capparis cartilaginea four isothiocynates were isolated and identified using GC and EI/MS techniques. These compounds were butyl isothiocyanate (1), 6-methylsulphonylhexyl isothiocyanate (2), 7-methylsulphonylheptyl isothiocyanate (3) and 5-benzylsulphonyl-4-pentenyl isothiocyanate (4). In addition to compounds (1) and (2), two other compounds were isolated and identified from Capparis deserti. These compounds are 3-methylthiopropyl isothiocyanate (5) and [11-(2-butenylthio)6-undecenyl isothiocyanate] (6). Compounds (1), (2), (5) and (6) are reported in this study for the first time from Capparis deserti. The main flavonoid component in the studied species was isolated and identified as rutin by comparing the data with those reported. Also, quantitative evaluation of rutin in the two species was carried out by TLC-densitometric analysis. The antioxidant activity was done using diphenylpicrylhydrazyl (DPPH) radical scavenging method. The butanol fraction from C. cartilaginea and C. deserti showed the highest antioxidant properties.

Naphthaquinones of Alkanna orientalis (L.) Boiss.

The roots of Alkanna orientalis (L.) Boiss yielded alpha-methyl-n-butyl alkannin (compound 1) and alkannin acetate (compound 2). The compounds were identified by UV, MS, (1)H NMR and (13)C NMR. Quantitative determination of alpha-methyl-n-butyl alkannin and alkannin acetate in Alkanna orientalis (L) Boiss roots was established by TLC densitometry.