subsp. Ethanolic Extract Indicated In Vitro Anti- Effect.

This study aims to investigate three endemic ethanolic leaf extracts from Cyprus for anti- activities: subsp. (Boiss.) Bolliger, subsp.

Alkaloids Isolated from Vepris glandulosa with Antidiabetic Properties: An In Vitro and In Silico Analysis.

Diabetes is a major global health issue and as current treatments fail, the search for new antidiabetic drugs is crucial. This investigation, focusing on identifying potential antidiabetic compounds from the endangered plant species Vepris glandulosa, led to the isolation of two known alkaloids, choisyine acetate (1) and choisyine (2). The study established the in vitro inhibitory activities and in silico molecular interaction of the two alkaloids with α-amylase based on IC values, Linewaever-Burk/Dixon plot kinetic analyses and Molecular docking, respectively.

Biflavonoids and bi- and tricoumarins from Daphne mezereum and inhibition of TNF-α secretion.

Daphne mezereum L. (Thymelaeaceae) was an important medicinal plant in Norway during the 18th and 19th centuries and used against diseases such as diarrhea, swelling, stomach pain, and tuberculosis. Five previously undescribed phenolic compounds, including two biflavonoids with a catechin core structure, two tricoumarins, and one bicoumarin, together with ten known compounds were isolated from a 50% EtOH extract of the bark of D.

Sandalwood Oils of Different Origins Are Active In Vitro against , the Major Fungal Pathogen Responsible for Eumycetoma.

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against , the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of (Santalaceae), i.e.

L.: Doesn't Origin Matter?

L. (Asteraceae) has a long and successful tradition in Europe as herbal medicine. Arnica flowers (i.

Chemical Constituents from Stem Bark and Their Antimicrobial Activities.

The phytochemical investigation of the ethylacetate fraction of an ethanolic extract obtained from the stem bark of (Moraceae) led to the isolation of four flavonoids: (2)-eriodictyol (), 2'- hydroxygenistein (), erycibenin A (), and genistein (); a dihydrobenzofuran: moracin P (); a coumarin: peucedanol (); and an apocarotenoid terpenoid: dihydrophaseic acid (). These were identified via 1D and 2D nuclear magnetic resonance spectroscopy (NMR) and ultra-high-resolution liquid chromatography-quadrupole time-of-flight mass spectroscopy (UHPLC-QTOF MS). Moracin P () is being reported for the first time in the genus while the others are known compounds ( and ) isolated previously from the genus but being reported for the first time from the species .

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics.

Natural products (NPs) from plants, fungi, animals, and microorganisms have historically played important roles in drug discovery [...

A QSAR Study for Antileishmanial 2-Phenyl-2,3-dihydrobenzofurans .

Leishmaniasis, a parasitic disease that represents a threat to the life of millions of people around the globe, is currently lacking effective treatments. We have previously reported on the antileishmanial activity of a series of synthetic 2-phenyl-2,3-dihydrobenzofurans and some qualitative structure-activity relationships within this set of neolignan analogues. Therefore, in the present study, various quantitative structure-activity relationship (QSAR) models were created to explain and predict the antileishmanial activity of these compounds.

Natural Products with Antitumor Potential Targeting the MYB-C/EBPβ-p300 Transcription Module.

The transcription factor MYB is expressed predominantly in hematopoietic progenitor cells, where it plays an essential role in the development of most lineages of the hematopoietic system. In the myeloid lineage, MYB is known to cooperate with members of the CCAAT box/enhancer binding protein (C/EBP) family of transcription factors. MYB and C/EBPs interact with the co-activator p300 or its paralog CREB-binding protein (CBP), to form a transcriptional module involved in myeloid-specific gene expression.

Sesquiterpene Lactones with Dual Inhibitory Activity against the Pteridine Reductase 1 and Dihydrofolate Reductase.

The parasite (. ) is responsible for human African trypanosomiasis (HAT) and the cattle disease "Nagana" which to this day cause severe medical and socio-economic issues for the affected areas in Africa. So far, most of the available treatment options are accompanied by harmful side effects and are constantly challenged by newly emerging drug resistances.

Investigation of the Variability of Alkaloids in L. Using Multivariate Data Analysis of LC/MS Profiles.

L. is a common ornamental plant in southern and central Europe, and has been used ethopharmacologically against a wide variety of diseases due to it containing -triterpene alkaloids of the -cycloartane type. Recently, we demonstrated the interesting antiprotozoal potential of some of these compounds.

Cyanogenesis in Aralia spinosa (Araliaceae).

A systematic survey of (Araliaceae), covering an entire growing season and including aboveground organs at various developmental stages, revealed that only about half of all samples collected showed cyanogenesis. Cyanogenesis was detected in inflorescences and leaves but is apparently restricted to certain harvest times or developmental stages. The structurally unusual triglochinin, characterized by a hex-2-enedioic acid partial structure, was the only cyanogenic glycoside detected.

Identification of Antiprotozoal Compounds from L. by PLS-Prediction.

Various -triterpene alkaloids of () L. have shown remarkable in vitro activity against the causative agents of tropical malaria and East African sleeping sickness. To identify further antiprotozoal compounds of this plant, 20 different fractions of .

Quantitative Structure-Activity Relationships of Natural-Product-Inspired, Aminoalkyl-Substituted 1-Benzopyrans as Novel Antiplasmodial Agents.

On the basis of the finding that various aminoalkyl-substituted chromene and chromane derivatives possess strong and highly selective in vitro bioactivity against , the pathogen responsible for tropical malaria, we performed a structure-activity relationship study for such compounds. With structures and activity data of 52 congeneric compounds from our recent studies, we performed a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) approach as implemented in the Open3DQSAR software. The resulting model displayed excellent internal and good external predictive power as well as good robustness.

Antiprotozoal -Triterpene Alkaloids from L.

Malaria and human African trypanosomiasis (HAT; sleeping sickness) are life-threatening tropical diseases caused by protozoan parasites. Due to limited therapeutic options, there is a compelling need for new antiprotozoal agents. In a previous study, O-tigloylcyclovirobuxeine-B was recovered from a .

L.: Antitrypanosomal Activity and Active Constituents against .

As part of our studies on antiprotozoal activity of approved herbal medicinal products, we previously found that a commercial tincture from L. (common Sage, Lamiaceae) possesses high activity against , causative agent of East African Human Trypanosomiasis. We have now investigated in detail the antitrypanosomal constituents of this preparation.

The Alkaloid-Enriched Fraction of (Buxaceae) Shows Prominent Activity against .

In the course of our studies on antiprotozoal natural products and following our recent discovery that certain aminosteroids and aminocycloartanoid compounds from A. DC. (Apocynaceae) and L.

Target-Guided Isolation of -tigloylcyclovirobuxeine -B from L. by Centrifugal Partition Chromatography.

The increasing drug resistance of malaria parasites challenges the treatment of this life-threatening disease. Consequently, the development of innovative and effective antimalarial drugs is inevitable. -tigloylcyclovirobuxeine-B, a -cycloartane alkaloid from L.

Natural Sesquiterpene Lactones of the 4,15--Atriplicolide Type are Inhibitors of Trypanothione Reductase.

In the course of our investigations on the antitrypanosomal potential of sesquiterpene lactones (STL), we have recently reported on the exceptionally strong activity of 4,15--Atriplicolide tiglate, which demonstrated an IC value of 15 nM against , the etiologic agent responsible for East African human trypanosomiasis (HAT). Since STLs are known to often interact with their biological targets (e.g.

Preparation of Sesquiterpene Lactone-Loaded PLA Nanoparticles and Evaluation of Their Antitrypanosomal Activity.

Human African trypanosomiasis (HAT), also commonly known as sleeping sickness, is a neglected tropical disease affecting millions of people in poorly developed regions in sub-Saharan Africa. There is no satisfactory treatment for this infection. The investment necessary to bring new drugs to the market is a big deterrent to drug development, considering that the affected communities form a non-lucrative sector.

Antitrypanosomal Activity of Sesquiterpene Lactones from L. Including a New Furanoheliangolide with an Unusual Structure.

As part of our efforts to exploit the antitrypanosomal potential of sesquiterpene lactones (STL) from L. (Asteraceae), besides the known 4,15--atriplicolide tiglate, -methacrylate and -isobutyrate, a hitherto unknown STL was isolated. Its structure was solved by extensive NMR measurements and confirmed by single crystal X-ray crystallography.

Potent Antitrypanosomal Activities of 3-Aminosteroids against African Trypanosomes: Investigation of Cellular Effects and of Cross-Resistance with Existing Drugs.

Treatment of animal African trypanosomiasis (AAT) requires urgent need for safe, potent and affordable drugs and this has necessitated this study. We investigated the trypanocidal activities and mode of action of selected 3-aminosteroids against . The in vitro activity of selected compounds of this series against (Savannah-type, IL3000), (bloodstream trypomastigote, Lister strain 427 wild-type (427WT)) and various multi-drug resistant cell lines was assessed using a resazurin-based cell viability assay.

Complementary Quantitative Structure⁻Activity Relationship Models for the Antitrypanosomal Activity of Sesquiterpene Lactones.

Three complementary quantitative structure⁻activity relationship (QSAR) methodologies, namely, regression modeling based on (i) "classical" molecular descriptors, (ii) 3D pharmacophore features, and (iii) 2D molecular holograms (HQSAR) were employed on the antitrypanosomal activity of sesquiterpene lactones (STLs) toward , the causative agent of the East African form of human African trypanosomiasis. In this study, an extension of a previous QSAR study on 69 STLs, models for a much larger and more diverse set of such natural products, now comprising 130 STLs of various structural subclasses, were established. The extended data set comprises a variety of STLs isolated and tested for antitrypanosomal activity within our group and is furthermore enhanced by 12 compounds obtained from literature, which have been tested in the same laboratory under identical conditions.

Natural products as inhibitors of Leishmania major dihydroorotate dehydrogenase.

The flavoenzyme dihydroorotate dehydrogenase (DHODH) catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which exerts vital functions in the cells, especially within DNA and RNA biosynthesis. Thus, this enzyme stands out as a new key molecular target for parasites causing Neglected Diseases (NDs). Focused on contributing to the development of new therapeutic alternatives for NDs, in this study, for the first time, a screening of 57 natural products for in vitro inhibition of Leishmania major DHODH (LmDHODH) was carried out, including cross validation against the human DHODH (HsDHODH).

A 3D-QSAR Study on the Antitrypanosomal and Cytotoxic Activities of Steroid Alkaloids by Comparative Molecular Field Analysis.

As part of our research for new leads against human African trypanosomiasis (HAT), we report on a 3D-QSAR study for antitrypanosomal activity and cytotoxicity of aminosteroid-type alkaloids recently isolated from the African medicinal plant A. DC. (Apocynaceae), some of which are strong trypanocides against (), with low toxicity against mammalian cells.