Natural Phenolic Compounds with Antithrombotic and Antiplatelet Effects: A Drug-likeness Approach.

BACKGROUND: Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessel diseases. Several studies have been conducted to identify antithrombotic agents from medicinal plants, and phenolic compounds (PCs) have been shown to effectively inhibit plasma coagulation and platelet aggregation. OBJECTIVES: This study aimed to conduct a survey of the natural PCs with proven antithrombotic and antiplatelet activities, as well as to evaluate by computational modeling the physicochemical and toxicological properties of these compounds using drug-likeness approaches. METHODS: The data were collected from the scientific database: 'Web of Science', 'Scifinder', 'Pubmed', 'ScienceDirect' and 'Google Scholar', the different classes of PCs with antithrombotic or antiplatelet effects were used as keywords. These molecules were also evaluated for their Drug-Likeness properties and toxicity to verify their profile for being candidates for new antithrombotic drugs. RESULTS: In this review, it was possible to register 85 lignans, 73 flavonoids, 28 coumarins, 21 quinones, 23 phenolic acids, 8 xanthones and 8 simple phenols. Activity records for tannins were not found in the researched databases. Of these 246 compounds, 213 did not violate any of Lipinski's rules of five, of which 125 (59%) showed non-toxicity, being promising candidates for new potential antithrombotic drugs. CONCLUSION: This review arouses interest in the isolation of phenolic compounds that may allow a new approach for the prevention of both arterial and venous thrombosis, with the potential to become alternatives in the prevention and treatment of cardiovascular diseases.

Anti-Inflammatory Activity of Lauraceae Plant Species and Prediction Models Based on Their Metabolomics Profiling Data.

The Lauraceae is a botanical family known for its anti-inflammatory potential. However, several species have not yet been studied. Thus, this work aimed to screen the anti-inflammatory activity of this plant family and to build statistical prediction models. The methodology was based on the statistical analysis of high-resolution liquid chromatography coupled with mass spectrometry data and the ex vivo anti-inflammatory activity of plant extracts. The ex vivo results demonstrated significant anti-inflammatory activity for several of these plants for the first time. The sample data were applied to build anti-inflammatory activity prediction models, including the partial least square acquired, artificial neural network, and stochastic gradient descent, which showed adequate fitting and predictive performance. Key anti-inflammatory markers, such as aporphine and benzylisoquinoline alkaloids were annotated with confidence level 2. Additionally, the validated prediction models proved to be useful for predicting active extracts using metabolomics data and studying their most bioactive metabolites.

Understanding the Seasonal Effect of Metabolite Production in Terminalia catappa L. Leaves through a Concatenated MS- and NMR-Based Metabolomics Approach.

Terminalia catappa L. (Combretaceae) is a medicinal plant that is part of the Brazilian biodiversity; this plant is popularly used for the treatment of a wide range of diseases. To better understand the chemical composition of T. catappa in different seasons, we conducted a thorough study using LC-MS and NMR data analysis techniques. The study helped obtain a chemical profile of the plant ethanolic extracts in different seasons of the year (spring, summer, autumn, and winter). The dereplication of LC-HRMS data allowed the annotation of 90 compounds in the extracts of T. catappa (hydrolyzable tannins, ellagic acid derivatives, and glycosylated flavonoids). Triterpenes and C-glycosyl flavones were the compounds that significantly contributed to differences observed between T. catappa plant samples harvested in autumn/winter and spring, respectively. The variations observed in the compound composition of the plant leaves may be related to processes induced by environmental stress and leaf development. Data fusion applied in the metabolomic profiling study allowed us to identify metabolites with greater confidence, and provided a better understanding regarding the production of specialized metabolites in T. catappa leaves under different environmental conditions, which may be useful to establish appropriate quality criteria for the standardization of this medicinal plant.

Genus Salsola: Chemistry, Biological Activities and Future Prospective-A Review.

The genus Salsola L. (Russian thistle, Saltwort) includes halophyte plants and is considered one of the largest genera in the family Amaranthaceae. The genus involves annual semi-dwarf to dwarf shrubs and woody tree. The genus Salsola is frequently overlooked, and few people are aware of its significance. The majority of studies focus on pollen morphology and species identification. Salsola has had little research on its phytochemical makeup or biological effects. Therefore, we present this review to cover all aspects of genus Salsola, including taxonomy, distribution, differences in the chemical constituents and representative examples of isolated compounds produced by various species of genus Salsola and in relation to their several reported biological activities for use in folk medicine worldwide.

UHPLC-(ESI)-HRMS and NMR-Based Metabolomics Approach to Access the Seasonality of Byrsonima intermedia and Serjania marginata From Brazilian Cerrado Flora Diversity.

Seasonality is one of the major environmental factors that exert influence over the synthesis and accumulation of secondary metabolites in medicinal plants. The application of the metabolomics approach for quality control of plant extracts is essentially important because it helps one to establish a standard metabolite profile and to analyze factors that affect the effectiveness of the medicinal plants. The Brazilian Cerrado flora is characterized by a rich diversity of native plant species, and a number of these plant species have been found to have suitable medicinal properties. Some of these plant species include Byrsonima intermedia and Serjania marginata. To better understand the chemical composition of these plant species, we conducted a study using the state-of-the-art techniques including the HPLC system coupled to an Exactive-Orbitrap high resolution mass spectrometer with electrospray ionization interface UHPLC-(ESI)-HRMS and by NMR being performed 2D J-resolved and proton NMR spectroscopy. For the analysis, samples were harvested bimonthly during two consecutive years. UHPLC-(ESI)-HRMS data were preprocessed and the output data uploaded into an in-house Excel macro for peak dereplication. MS and NMR data were concatenated using the data fusion method and submitted to multivariate statistical analysis. The dereplication of LC-HRMS data helped in the annotation of the major compounds present in the extracts of the three plant species investigated allowing the annotation of 68 compounds in the extracts of B. intermedia (cinnamic acids, phenolic acids derived from galloyl quinic and shikimic acid, proanthocyanidins, glycosylated flavonoids, triterpenes and other phenols) and 81 compounds in the extracts of S. marginata (phenolic acids, saponins, proanthocyanidins, glycosylated flavonoids among other compounds). For a better assessment of the great number of responses, the significance of the chemical variables for the differentiation and correlation of the seasons was determined using the variable importance on projection (VIP) technique and through the application of the false discovery rate (FDR) estimation. The statistical data obtained showed that seasonal factors played an important role on the production of metabolites in each plant species. Temperature conditions, drought and solar radiation were found to be the main factors that affected the variability of phenolic compounds in each species.

Thyme (Thymus vulgaris [Lamiaceae]) Leaves Inhibit Contraction of the Nonpregnant Mouse Uterus.

Dysmenorrhea is painful menstrual periods, which affects 25% of women within reproductive age and has a prevalence of 67.2-90.0%. Current treatment has several adverse effects and can be ineffective once the pain is initiated. Thymus vulgaris traditionally used for pain management was investigated in this study for its activity on uterine contraction in the nonpregnant uterus, as a parameter for dysmenorrhea. The dried leaves of T. vulgaris were macerated in water, and the resulting aqueous extract was investigated on the isolated mouse uterus. Parameters investigated included spontaneous contractions, oxytocin-induced contractions, and high potassium chloride (KCl; 80 mM)-induced tonic contractions. Mass spectrometric analysis of the thyme extract was also performed using liquid chromatography-high-resolution Fourier Transform mass spectrometry. Thyme extract inhibited the amplitude and frequency of spontaneous and oxytocin-induced uterine contractions. It also inhibited KCl-induced tonic contractions. The activities observed suggest that T. vulgaris inhibits uterine contractions through blockade of extracellular voltage-gated calcium channels. Secondary metabolites detected included compounds belonging to chlorogenic phytochemical class and flavonoids, which are known to have activities on extracellular calcium blockade. This study has shown that aqueous T. vulgaris extract, also known as thyme, inhibits contractions of the nonpregnant uterus and can be a lead plant in the drug discovery process for the management of dysmenorrhea.

Targeted Isolation of Anti-Trypanosomal Naphthofuran-Quinone Compounds from the Mangrove Plant Avicennia lanata.

The discovery of new secondary metabolites from natural origins has become more challenging in natural products research. Different approaches have been applied to target the isolation of new bioactive metabolites from plant extracts. In this study, bioactive natural products were isolated from the crude organic extract of the mangrove plant Avicennia lanata collected from the east coast of Peninsular Malaysia in the Setiu Wetlands, Terengganu, using HRESI-LCMS-based metabolomics-guided isolation and fractionation. Isolation work on the crude extract A. lanata used high-throughput chromatographic techniques to give two new naphthofuranquinone derivatives, hydroxyavicenol C (1) and glycosemiquinone (2), along with the known compounds avicenol C (3), avicequinone C (4), glycoquinone (5), taraxerone (6), taraxerol (7), ß-sitosterol (8) and stigmasterol (9). The elucidation and identification of the targeted bioactive compounds used 1D and 2D-NMR and mass spectrometry. Except for 6-9, all isolated naphthoquinone compounds (1-5) from the mangrove plant A. lanata showed significant anti-trypanosomal activity on Trypanosoma brucei brucei with MIC values of 3.12-12.5 µM. Preliminary cytotoxicity screening against normal prostate cells (PNT2A) was also performed. All compounds exhibited low cytotoxicity, with compounds 3 and 4 showing moderate cytotoxicity of 78.3% and 68.6% of the control values at 100 µg/mL, respectively.

Tocolytic activity assessment of the methanol leaf extract of Justicia flava Vahl (Acanthaceae) on mouse myometrial contractility and preliminary mass spectrometric determination of secondary metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Justicia flava are traditionally used in the South of Nigeria to prevent preterm births. AIM OF THE STUDY: In this study, the activity of the methanol leaf extract of J. flava (JF) was investigated on uterine contractility in non-pregnant and pregnant isolated mouse tissues. MATERIAL AND METHODS: The effects on spontaneous, oxytocin, and KCl-induced contractions were determined. The effects in calcium-free media were also determined. Possible mechanisms of activity were investigated using receptor and channel modulators. Mass spectrometric analysis was additionally performed on the leaf extract to identify secondary metabolites. RESULTS: JF was observed to inhibit spontaneous, oxytocin and high KCl-induced uterine contractility. JF also inhibited contractions in Ca2+-free media. JF was found to exert its inhibitory effect via interaction with inositol triphosphate and ryanodine receptors and also through modulation of K+- channels. Lignans and alkaloids were identified with the lignans being the most abundant in JF. CONCLUSION: JF has been shown to potently inhibit uterine contractions in non-pregnant and pregnant isolated mouse uterus. The inhibitory activity of JF has been shown to occur via blockade of extracellular and intracellular calcium entry and these effects may be due to the lignans identified in - JF. JF has therefore been shown in this study to be a lead plant in the discovery of new drugs with uterine inhibitory activity.

Application of metabolomics and molecular networking in investigating the chemical profile and antitrypanosomal activity of British bluebells (Hyacinthoides non-scripta).

Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filtration and considering their previously reported bioactivities. Molecular networking was implemented to look for similarities in fragmentation patterns between the isolated saponin glycoside at m/z 1445.64 [M + formic-H]- equivalent to C64H104O33 and the putatively found active metabolite at m/z 1283.58 [M + formic-H]- corresponding to scillanoside L-1. A combination of metabolomics and bioactivity-guided approaches resulted in the isolation of a norlanostane-type saponin glycoside with antitrypanosomal activity of 98.9% inhibition at 20 µM.

Isolation of anticancer and anti-trypanosome secondary metabolites from the endophytic fungus Aspergillus flocculus via bioactivity guided isolation and MS based metabolomics.

This study aims to identify bioactive anticancer and anti-trypanosome secondary metabolites from the fermentation culture of Aspergillus flocculus endophyte assisted by modern metabolomics technologies. The endophyte was isolated from the stem of the medicinal plant Markhamia platycalyx and identified using phylogenetics. Principle component analysis was employed to screen for the optimum growth endophyte culturing conditions and revealing that the 30-days rice culture (RC-30d) provided the highest levels of the bioactive agents. To pinpoint for active chemicals in endophyte crude extracts and successive fractions, a new application of molecular interaction network is implemented to correlate the chemical and biological profiles of the anti-trypanosome active fractions to highlight the metabolites mediating for bioactivity prior to purification trials. Multivariate data analysis (MVDA), with the aid of dereplication studies, efficiently annotated the putatively active anticancer molecules. The small-scale RC-30d fungal culture was purified using high-throughput chromatographic techniques to yield compound 1, a novel polyketide molecule though inactive. Whereas, active fractions revealed from the bioactivity guided fractionation of medium scale RC-30d culture were further purified to yield 7 metabolites, 5 of which namely cis-4-hydroxymellein, 5-hydroxymellein, diorcinol, botryoisocoumarin A and mellein, inhibited the growth of chronic myelogenous leukemia cell line K562 at 30 µM. 3-Hydroxymellein and diorcinol exhibited a respective inhibition of 56% and 97% to the sleeping sickness causing parasite Trypanosoma brucei brucei. More interestingly, the anti-trypanosomal activity of A. flocculus extract appeared to be mediated by the synergistic effect of the active steroidal compounds i.e. ergosterol peroxide, ergosterol and campesterol. The isolated structures were elucidated by using 1D, 2D NMR and HR-ESIMS.

Identification of GSK-3 as a Potential Therapeutic Entry Point for Epilepsy.

In view of the clinical need for new antiseizure drugs (ASDs) with novel modes of action, we used a zebrafish seizure model to screen the anticonvulsant activity of medicinal plants used by traditional healers in the Congo for the treatment of epilepsy, and identified a crude plant extract that inhibited pentylenetetrazol (PTZ)-induced seizures in zebrafish larvae. Zebrafish bioassay-guided fractionation of this anticonvulsant Fabaceae species, Indigofera arrecta, identified indirubin, a compound with known inhibitory activity of glycogen synthase kinase (GSK)-3, as the bioactive component. Indirubin, as well as the more potent and selective GSK-3 inhibitor 6-bromoindirubin-3'-oxime (BIO-acetoxime) were tested in zebrafish and rodent seizure assays. Both compounds revealed anticonvulsant activity in PTZ-treated zebrafish larvae, with electroencephalographic recordings revealing reduction of epileptiform discharges. Both indirubin and BIO-acetoxime also showed anticonvulsant activity in the pilocarpine rat model for limbic seizures and in the 6-Hz refractory seizure mouse model. Most interestingly, BIO-acetoxime also exhibited anticonvulsant actions in 6-Hz fully kindled mice. Our findings thus provide the first evidence for anticonvulsant activity of GSK-3 inhibition, thereby implicating GSK-3 as a potential therapeutic entry point for epilepsy. Our results also support the use of zebrafish bioassay-guided fractionation of antiepileptic medicinal plant extracts as an effective strategy for the discovery of new ASDs with novel mechanisms of action.

Metabolomic-Guided Isolation of Bioactive Natural Products from Curvularia sp., an Endophytic Fungus of Terminalia laxiflora.

Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology. Metabolomic tools were successfully employed to compare the metabolite fingerprints of solid and liquid culture extracts of endophyte Curvularia sp. isolated from the leaves of Terminalia laxiflora. Natural product databases were used to dereplicate metabolites in order to determine known compounds and the presence of new natural products. Multivariate analysis highlighted the putative metabolites responsible for the bioactivity of the fungal extract and its fractions on NF-κB and the myelogenous leukemia cell line K562. Metabolomic tools and dereplication studies using high-resolution electrospray ionization mass spectrometry directed the fractionation and isolation of the bioactive components from the fungal extracts. This resulted in the isolation of N-acetylphenylalanine (1: ) and two linear peptide congeners of 1: : dipeptide N-acetylphenylalanyl-L-phenylalanine (2: ) and tripeptide N-acetylphenylalanyl-L-phenylalanyl-L-leucine (3: ).

Metabolomic Tools to Assess the Chemistry and Bioactivity of Endophytic Aspergillus Strain.

Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology that may find applications as pharmaceutical and agrochemical drugs. In this study, a combination of metabolomics and bioactivity-guided approaches were employed to isolate secondary metabolites with cytotoxicity against cancer cells from an endophytic Aspergillus aculeatus. The endophyte was isolated from the Egyptian medicinal plant Terminalia laxiflora and identified using molecular biological methods. Metabolomics and dereplication studies were accomplished by utilizing the MZmine software coupled with the universal Dictionary of Natural Products database. Metabolic profiling, with aid of multivariate data analysis, was performed at different stages of the growth curve to choose the optimized method suitable for up-scaling. The optimized culture method yielded a crude extract abundant with biologically-active secondary metabolites. Crude extracts were fractionated using different high-throughput chromatographic techniques. Purified compounds were identified by HR-ESI-MS, 1D- and 2D-NMR. This study introduced a new method of dereplication utilizing both high-resolution mass spectrometry and NMR spectroscopy. The metabolites were putatively identified by applying a chemotaxonomic filter. We also present a short review on the diverse chemistry of terrestrial endophytic strains of Aspergillus, which has become a part of our dereplication work and this will be of wide interest to those working in this field.

Characterisation of the antiproliferative constituents and activity of Ficus exasperata (Vahl) on ovarian cancer cells -a preliminary investigation.

Ovarian cancer is one of the most common gynaecological cancers today. This study therefore investigates the anticancer effects of Ficus exasperata extracts and fractions on ovarian cancer cells. The antiproliferative activity of the crude extracts (1 mg/mL) was assessed using the MTT assay on A2780 (ovarian cancer) cell line. Bio-activity guided fractionation was performed and preliminary identification was further achieved using high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. All crude extracts tested exhibited antiproliferative activity except for the methanol extract which interestingly showed proliferative effects. Five fatty acids were identified from the active fractions (FB1-10 and FB1-12). FB1-12 exhibited an IC50 value of 15.20 µg/mL. The least potent fraction (FB1-4 + 5) had an IC50 value of 34.51 µg/mL. H1-HEX and H1-MET exhibited 97.2 and 97.9%, respectively, compared to control. This study therefore provides proof-of-principle that fatty acids of Ficus exasperata exhibit significant antiproliferative effects on ovarian cancer cells.

Metabolomics-Guided Isolation of Anti-trypanosomal Metabolites from the Endophytic Fungus Lasiodiplodia theobromae.

Fungal endophytes offer diverse and unique secondary metabolites, making these organisms potential sources of promising drug leads. The application of high-resolution-liquid chromatography mass spectrometry and nuclear magnetic resonance-based metabolomics to fungal endophytes is practical in terms of dereplication studies and the mining of bioactive compounds. In this paper, we report the application of metabolomics in parallel with anti-trypanosomal assays to determine the ideal conditions for the medium-scale fermentation of the endophyte Lasiodiplodia theobromae. The 1H NMR comparison between the active versus inactive fractions identified several unique chemical fingerprints belonging to the active fractions. Furthermore, by integrating high-resolution-liquid chromatography mass spectrometry data with multivariate data analysis, such as orthogonal partial least squares-discriminant analysis (OPLS-DA) and the bioactivity results of the fractions of L. theobromae, the anti-trypanosomal agents were easily discerned. With available databases such as Antibase and Dictionary of Natural Products coupled to MZmine through in-house algorithms optimized in our laboratory, the predicted metabolites were readily identified prior to isolation. Fractionation was performed on the active fractions and three known compounds were isolated, namely, cladospirone B, desmethyl-lasiodiplodin, and R-(-)-mellein. Cladospirone B and desmethyl-lasiodiplodin were among the predicted compounds generated by the OPLS-DA S-plot, and these compounds exhibited good activity against Trypanosoma brucei brucei with minimum inhibitory concentrations of 17.8 µM and 22.5 µM, respectively.

Effect of the environment on the secondary metabolic profile of Tithonia diversifolia: a model for environmental metabolomics of plants.

Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant's metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts.

Isolation and characterization of cyclo-(tryptophanyl-prolyl) and chloramphenicol from Streptomyces sp. SUK 25 with antimethicillin-resistant Staphylococcus aureus activity.

BACKGROUND: Zingiber spectabile, commonly known as Beehive Ginger, is used as an ethnobotanical plant in many countries as an appetizer or to treat stomachache, toothache, muscle sprain, and as a cure for swelling, sores and cuts. This is the first report of isolation of Streptomyces strain from the root of this plant. Strain Universiti Kebangsaan 25 (SUK 25) has a very high activity to produce secondary metabolites against methicillin-resistant Staphylococcus aureus (MRSA), which is associated with high morbidity and mortality rates due to acquired multidrug resistance genes and causes medication failure in some clinical cases worldwide. Phylogenetic analysis based on the 16S ribosomal RNA gene sequence exhibited that the most closely related strain was Streptomyces omiyaensis NBRC 13449T (99.0% similarity). AIM: This study was conducted to carry out the extraction, identification, and biological evaluation of active metabolites isolated from SUK 25 against three MRSA strains, namely, MRSA ATCC 43300, MRSA ATCC 33591, and MRSA ATCC 49476. MATERIALS AND METHODS: The production of secondary metabolites by this strain was optimized through Thronton's media. Isolation, purification, and identification of the bioactive compounds were carried out using reversed-phase high-performance liquid chromatography, high-resolution mass spectrometry, Fourier transform infrared, and one-dimensional and two-dimensional nuclear magnetic resonance. RESULTS: During screening procedure, SUK 25 exhibited good antimicrobial potential against several strains of MRSA. The best biological activity was shown from fraction number VII and its subfractions F2 and F3 with minimum inhibitory concentration values at 16 µg/mL and 8 µg/mL, respectively. These two subfractions were identified as diketopiperazine cyclo-(tryptophanyl-prolyl) and chloramphenicol. CONCLUSION: On the basis of obtained results, SUK 25 isolated from Z. spectabile can be regarded as a new valuable source to produce secondary metabolites against bacteria, especially MRSA.

In vivo antimalarial activity of the endophytic actinobacteria, Streptomyces SUK 10.

Endophytic bacteria, such as Streptomyces, have the potential to act as a source for novel bioactive molecules with medicinal properties. The present study was aimed at assessing the antimalarial activity of crude extract isolated from various strains of actinobacteria living endophytically in some Malaysian medicinal plants. Using the four day suppression test method on male ICR strain mice, compounds produced from three strains of Streptomyces (SUK8, SUK10, and SUK27) were tested in vivo against Plasmodium berghei PZZ1/100 in an antimalarial screen using crude extracts at four different concentrations. One of these extracts, isolated from Streptomyces SUK10 obtained from the bark of Shorea ovalis tree, showed inhibition of the test organism and was further tested against P. berghei-infected mice for antimalarial activity at different concentrations. There was a positive relationship between the survival of the infected mouse group treated with 50 µg/kg body weight (bw) of ethyl acetate-SUK10 crude extract and the ability to inhibit the parasites growth. The parasite inhibition percentage for this group showed that 50% of the mice survived for more than 90 days after infection with the parasite. The nucleotide sequence and phylogenetic tree suggested that Streptomyces SUK10 may constitute a new species within the Streptomyces genus. As part of the drug discovery process, these promising finding may contribute to the medicinal and pharmaceutical field for malarial treatment.

Antichlamydial sterol from the Red Sea sponge Callyspongia aff. implexa.

Marine sponges are rich sources of natural products exhibiting diverse biological activities. Bioactivity-guided fractionation of the Red Sea sponge Callyspongia aff. implexa led to the isolation of two new compounds, 26,27-bisnorcholest-5,16-dien-23-yn-3ß,7α-diol, gelliusterol E (1) and C27-polyacetylene, callimplexen A (2), in addition to the known compound ß-sitosterol (3). The structures of the isolated compounds were determined by 1D- and 2D-NMR techniques as well as high-resolution tandem mass spectrometry and by comparison to the literature. The three compounds (1-3) were tested against Chlamydia trachomatis, an obligate intracellular gram-negative bacterium, which is the leading cause of ocular and genital infections worldwide. Only gelliusterol E (1) inhibited the formation and growth of chlamydial inclusions in a dose-dependent manner with an IC50 value of 2.3 µM.

The re-emergence of natural products for drug discovery in the genomics era.

Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.