Two new rotenoid glycosides from the rhizomes of Stemona curtisii Hook. f.

Two new rotenoid glycosides named stemonal 11-O-ß-D-glucopyranoside and 6-O-methylstemonal 11-O-ß-D-glucopyranoside together with ten known metabolites were isolated from the rhizomes of Stemona curtisii. The chemical structures of the new compounds were elucidated based on the analysis of their 1D and 2D NMR and HRESIMS, while the sugar unit and absolute configuration were determined by chemical hydrolysis and ECD analysis. Among the tested compounds for anti-α-glucosidase assay, stemonal showed an inhibitory effect (IC50 = 38.67 µM), which is 2.4-fold more potent than acarbose. Cytotoxic evaluation against the lung adenocarcinoma A549 cell line indicated that none of the compounds were strongly active to suppress the cancer cell growth at 100 µM. This work describes the occurrence of rotenoids bearing a sugar moiety, which are reported for the first time in the genus Stemona. The isolated compound's α-glucosidase inhibitory potential provides insight for further investigation of natural rotenoids as anti-diabetic agents.

Two new phenolic compounds from Boerhavia erecta collected in Vietnam.

Boerhavia erecta is a tropical plant that is widely used in Asian folk medicine. Little is known about the alpha-glucosidase inhibition and antimicrobial properties of compounds from this plant. In the present study, the phytochemical study of the aerial parts of B. erecta collected in Vietnam was conducted using multiple chromatographic methods. The chemical structures of isolated compounds were identified by comprehensive spectroscopic methods. Two new compounds, berectone C (1) and (E)-tetracosyl 3-(3-hydroxy-4-methoxyphenyl)acrylate (4), together with the known compounds boeravinone C (2), liquiritigenin (3), bis(1H-indol-3-yl)methanone (5), and indole-3-carboxylic acid (6) were isolated and structural elucidated. Compounds 1 and 4 were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Compound 1 showed strong inhibition of the alpha-glucosidase enzyme (IC50 43 µg/mL). Only compound 1 exhibited antimicrobial property against A. baumannii, forming an inhibition zone of 11 mm.

Three new rotenoids from the stems of Derris elliptica and their anti-microbial activity.

Three new rotenoids, named derieliptosides A-C (1-3), were isolated from the stems of Derris elliptica (Wall.) Benth. Their structures were determined by HR-ESI-MS and NMR spectroscopic methods. Absolute configurations of them were elucidated by analysis of ECD spectra in comparison with TD-DFT calculation. Compounds 1-3 inhibited the growth of fungus Candida albicans and selectively inhibited bacterial strains. Of these, compound 1 showed selective inhibition on the growth of Enterococcus faecalis (MIC: 37.5 µM and IC50: 10.6 µM), Staphylococcus aureus (MIC: 75 µM and IC50: 22.7 µM), and C. albicans (MIC: 37.5 µM and IC50: 11.2 µM).

Berectones A and B: Two new rotenoids from the aerial parts of Boerhavia erecta.

Two previously unreported rotenoids, berectones A and B (1 and 2), along with four known compounds, 3,3',4'-tri-O-methylellagic acid (3), kaempferol (4), 7,4'-dihydroxy-8-methoxyisoflavone (5), and trans-N-caffeoyltyramine (6) were isolated from the aerial parts of Boerhavia erecta. The structures of all isolated compounds were fully characterized using spectroscopic data, as well as comparison with the previous literature. Compound 6 exhibited the strongest inhibitory activity toward α-glucosidase with IC50 value of 4.74 µM.[Formula: see text].

A Review on Rotenoids: Purification, Characterization and its Biological Applications.

Phytochemicals play a vital role as drugs for the treatment of various autoimmune, viral, and cancerous diseases. Rotenoids, a type of isoflavone compounds present in plants genus Boerhaavia sp., Mirabilis sp. and Abronia sp. which belong to the Nyctaginaceae family, are traditionally used as pesticides and insecticides. Boeravinones are groups of rotenoid compounds widely used as drugs or drug adjuvants for the treatment of various diseases. Extraction of rotenoids in various solvents, purification of rotenoids in various chromatographic technique studies, and the characterization of functional groups of rotenoids in various spectroscopic techniques have been reported. Biological applications of rotenoids such as anti-cancerous, antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities have been discussed. This review summarizes the extraction, isolation, purification, and characterization of rotenoid compounds and their effect on the treatment of cancer, inflammatory, spasmolytic, autoimmune, and microbial diseases.

Synthesis of 4-Acylchromene via Highly Chemoselective Iodine-Catalyzed Cyclization of Alkynylarylether Dimethylacetals.

4-Acylchromene is an important core structure found in bioactive natural products and bioactive synthetic compounds. Moreover, this core structure is frequently used as a key precursor for the synthesis of more complex molecules. In this work, we discovered that a combination of acetone and catalytic I2 could lead to selective activation of acetal in alkynylarylether dimethylacetal substrates while alkyne moiety remained intact. This activation of acetal led to the generation of oxonium ion intermediate which triggered intramolecular cyclization and elimination of methanol to provide the desired 4-acylchromene as the sole product in up to 95% yield. Moreover, this method could be applied in a broad range of substrates under a mild and metal-free catalytic conditions for the synthesis of 4-acylchromene derivatives.

Rotenoid and isoflavone metabolites from an antioxidant seed extract of Dalbergia lanceolaria subsp. paniculata (roxb.) thoth.

A new rotenoid named 12-O-methylrotenolol along with five known rotenoid and isoflavone metabolites were isolated from the seeds of Dalbergia lanceolaria subsp. paniculata, collected from Egypt. The structures of these compounds were identified by physical and spectroscopic data measurements ([α]D, UV, 1D- and 2D-NMR and MS). The methanol extract of the seeds exhibited strong antioxidant activity with IC50 value 0.7 µg/µl against DPPH radical, in respect to quercetin as antioxidant reference (IC50 1.5 µM), while the tested compounds from this extract showed weak activities with IC50 values ranged from 19.6 to 33.0 µM.

Promising Potential of Lonchocarpus utilis against South American Myasis.

Traditional medicine is especially important in the treatment of neglected tropical diseases because it is the way the majority of populations of affected countries manage primary healthcare. We present a case study that can serve as an example that can be replicated by others in the same situation. It is about the validation of a local remedy for myasis in Amazonian Ecuador, which is contrasted by bibliographic chemical reviews and in silico activity tests. We look for scientific arguments to demonstrate the reason for using extracts of Lonchocarpus utilis against south American myasis (tupe). We provide a summary of the isoflavonoids, prenylated flavonoids, chalcones, and stilbenes that justify the action. We make modeling predictions on the affinity of eight chemical components and enzyme targets using Swiss Target Prediction software. We conclude that the effects of this extract can be reasonably attributed to an effect of the parasite that causes the disease, similar to the one produced by synthetic drugs used by conventional medicine (e.g., Ivermectine).

Biopharmacological considerations for accelerating drug development of deguelin, a rotenoid with potent chemotherapeutic and chemopreventive potential.

Deguelin is a rotenoid compound that exists in abundant quantities in the bark, roots, and leaves of the Leguminosae family of plants. An analysis of evidence from both in vitro and in vivo studies suggests that deguelin displays potent anticancer activity against multiple cancer types and exhibits chemopreventive potential in Akt-inducible transgenic mouse models. Deguelin appears to impede carcinogenesis by enhancing cell apoptosis and hindering malignant transformation and tumor cell propagation. Crucial oncogenic pathways likely targeted by deguelin include the epithelial-to-mesenchymal transition; angiogenesis-related pathways; and the phosphoinositide 3-kinase/Akt, Wnt, epidermal growth factor receptor, c-Met, and hedgehog signal transduction cascades. This review article provides a comprehensive summary of current preclinical research featuring deguelin as a leading chemotherapeutic and chemopreventive compound, and it highlights the importance of identifying companion molecular biomarkers and performing systemic pharmacokinetic studies for accelerating the process of developing deguelin as a clinical anticancer agent.

Integrated Analysis of Transcriptomic and Proteomics Data Reveals the Induction Effects of Rotenoid Biosynthesis of Mirabilis himalaica Caused by UV-B Radiation.

Mirabilis himalaica (Edgew.) Heimerl is one of the most important genuine medicinal plants in Tibet, in which the special plateau habitat has been associated with its excellent medicinal quality and efficacy. However, the mechanisms by which environmental factors affect biosynthesis of secondary metabolic components remain unclear in this species. In this study, RNA sequencing and iTRAQ (isobaric Tags for Relative and Absolute Quantification) techniques were used to investigate the critical molecular "events" of rotenoid biosynthesis responding to UV-B radiation, a typical plateau ecological factor presented in native environment-grown M. himalaica plants. A total of 3641 differentially expressed genes (DEGs) and 106 differentially expressed proteins (DEPs) were identified in M. himalaica between UV-B treatment and control check (CK). Comprehensive analysis of protein and transcript data sets resulted in 14 and 7 DEGs from the plant hormone signal transduction and phosphatidylinositol signaling system pathways, respectively, being significantly enriched. The result showed that the plant hormone signal transduction and phosphatidylinositol signaling system might be the key metabolic strategy of UV-B radiation to improve the biosynthesis of rotenoid in M. himalaica. At same time, most of the DEGs were associated with auxin and calcium signaling, inferring that they might drive the downstream transmission of these signal transduction pathways. Regarding those pathways, two chalcone synthase enzymes, which play key roles in the biosynthesis of rotenoid that were thought as the representative medicinal component of M. himalaica, were significantly upregulated in UV-B radiation. This study provides a theoretical basis for further exploration of the adaptation mechanism of M. himalaica to UV-B radiation, and references for cultivation standardization.

Integrated analysis of transcriptomic and metabolomic data reveals critical metabolic pathways involved in rotenoid biosynthesis in the medicinal plant Mirabilis himalaica.

Mirabilis himalaica (Edgew.) Heimerl is among the most important genuine medicinal plants in Tibet. However, the biosynthesis mechanisms of the active compounds in this species are unclear, severely limiting its application. To clarify the molecular biosynthesis mechanism of the key representative active compounds, specifically rotenoid, which is of special medicinal value for M. himalaica, RNA sequencing and TOF-MS technologies were used to construct transcriptomic and metabolomic libraries from the roots, stems, and leaves of M. himalaica plants collected from their natural habitat. As a result, each of the transcriptomic libraries from the different tissues was sequenced, generating more than 10 Gb of clean data ultimately assembled into 147,142 unigenes. In the three tissues, metabolomic analysis identified 522 candidate compounds, of which 170 metabolites involved in 114 metabolic pathways were mapped to the KEGG. Of these genes, 61 encoding enzymes were identified to function at key steps of the pathways related to rotenoid biosynthesis, where 14 intermediate metabolites were also located. An integrated analysis of metabolic and transcriptomic data revealed that most of the intermediate metabolites and enzymes related to rotenoid biosynthesis were synthesized in the roots, stems and leaves of M. himalaica, which suggested that the use of non-medicinal tissues to extract compounds was feasible. In addition, the CHS and CHI genes were found to play important roles in rotenoid biosynthesis, especially, since CHS might be an important rate-limiting enzyme. This study provides a hypothetical basis for the screening of new active metabolites and the metabolic engineering of rotenoid in M. himalaica.

Brown Stink Bug Mortality by Seed Extracts of Tephrosia Vogelii Containing Deguelin and Tephrosin

ABSTRACT Extracts of the seeds of Tephrosia vogelii Hook. f. were studied in relation to its chemical composition and toxicity to the brown stink bug Euschistus heros (F.). The extracts were obtained in ethyl acetate and ethanol in the sequence according to the polar nature of the solvents. Extracts were sprayed in concentration of 1.0, 2.5, 5.0, 7.5 and 10% on third-instars nymphs and adults, and mortality was recorded. Presence two rotenoids in ethyl acetate was detected, with analyzed with gas chromatography-mass spectrometry (GC-MS). Crude fraction analyses confirmed the presence of these rotenoids (tephrosin - 2.71% in ethyl acetate and 3.66% in methanol; and deguelin - 10.46% in ethyl acetate and 1.22% in methanol) and three other rotenoids in small amounts. Eight days after applications, ethyl acetate caused more stink bugs mortality and on less time than ethanol extract, because great quantity of rotenoids, as polarity. Concentrations above to 1 and 2.5% of the ethyl acetate extracts caused mortality above 80% of the nymphs and adults of E. heros, respectively. Concentration were considered high, thus chemist analyzes demonstrated high rotenoids presence. In conclusion, seed T. vogelli extracts, rich in deguelin and tephrosin (3:1), cause mortality of E. heros, however, high concentration are necessary.

Screening of a small, well-curated natural product-based library identifies two rotenoids with potent nematocidal activity against Haemonchus contortus.

The control of parasitic roundworms (nematodes) is heavily reliant on the use of a limited number of anthelmintic drugs. However, drug resistance is now very widespread and no vaccines are available, such that the discovery of new chemical entities is crucial. Within this context, we screened a library of pure natural products (n=400) against exsheathed third-stage (xL3) larvae of the parasitic nematode Haemonchus contortus using a whole-organism screening method. We identified two plant-derived rotenoids, deguelin and rotenone, with inhibitory activity on xL3 motility. Rotenone was not investigated further, because of its toxicity to some vertebrates. The dose response and cytotoxicity studies showed potent and selective inhibitory activity of deguelin on motility of xL3 larvae of H. contortus. Detailed future work needs to be conducted to explore the mode of action of this compound on H. contortus and related nematodes, and to assess its potential as an anthelmintic candidate.

Cytotoxic rotenoid glycosides from the seeds of Amorpha fruticosa.

Four new rotenoid glycosides, namely amorphaside A-D (1-4), along with four known ones (5-8) were isolated from the seeds of Amorpha fruticosa. Their chemical structures and absolute configurations were elucidated by HRESIMS, NMR and CD spectra, as well as deduction from biosynthesis route. The sugar units were determined by acid hydrolysis, appropriate derivatization and HPLC analysis. The in vitro anti-proliferative activities of all compounds were evaluated against MCF-7 and HCT-116 cell lines. The results showed that compounds 1-3 had no effect on cell proliferation in the two cell lines even with the concentration of 50 µM, and compounds 4, 7 and 8 had selective cytotoxicity against MCF-7 with IC50 values of 3.90, 0.95 and 34.08 µM, respectively, while compounds 5 and 6 both showed significant cytotoxicity to the two cell lines with IC50 values less than 2.00 µM, even better than the positive control cisplatin. These preliminary results indicated that compounds 5 and 6 might be valuable to anticancer drug candidates.

A dehydrorotenoid produced by callus tissue culture and wild plant roots of Boerhaavia coccinea

Calli cultures were established from leaves and stem of B. coccinea plantlet produced in vitro and analysed for isoflavonoid content. The quantification of 6,9,11-trihydroxy-6a,12a-dehydrorotenoid isolated from the roots of Boerhaavia coccinea P. Miller collected from its natural environment, and the same metabolite produced in callus tissue culture of the same plant are described in this paper. The rotinary quantitative HPLC analysis indicated that callus culture produced the same isoflavonoid compound found in the roots of intact wild growing plant. The amount of the secondary metabolite produced in vitro was 955.35 µg/g of dry cell weight, 2.5 times more than the highest amount concentration produced by the wild growing plant in its natural environment.

Cultura de calos foram estabelecidos de folhas e galhos finos de plântula de B. coccinea produzida in vitro e analisada para isoflavonóide. A quantificação do 6,9,11-triidroxi-6a,12a-desidro-rotenóide isolado das raízes de B. coccinea P Miller, coletada em seu habitat natural, e do mesmo rotenóide produzido na cultura de células estão descritos neste artigo. A análise rotineira em CLAE mostrou que a cultura de calos produziu o mesmo isoflavonóide encontrado nas raízes da planta do campo. A quantidade do metabólito secundário produzido in vitro foi de 955.35 µg/g de massa seca de callus, atingindo uma concentração de 2,5 vezes maior do que a quantidade do metabólito produzido pela planta em seu meio ambiente natural.