zur Suche springenzur Navigation springenzum Inhalt springen

Publikationen - Natur- und Wirkstoffchemie

Sortieren nach: Erscheinungsjahr Typ der Publikation

Zeige Ergebnisse 1 bis 9 von 9.

Publikation

Al-kaf, A. G.; Crouch, R. A.; Denkert, A.; Porzel, A.; Al-Hawshabi, O. S. S.; Ali, N. A. A.; Setzer, W. N.; Wessjohann, L.; Chemical composition and biological activity of essential oil of Chenopodium ambrosioides from Yemen Am. J. Essent. Oils Nat. Prod. 4, 20-22, (2016)

The chemical composition of the hydrodistilled leaf essential oil from Chenopodium ambrosioides L. growing wild in Yemen was determined by GC-MS analysis, and its cytotoxic, and general antioxidant potential were evaluated. Major compounds of C. ambrosioides oil were ascaridole (54.2%), isoascaridole (27.7%) and p-cymene (8.1%). At concentrations of 50 and 25 μg/mL, the essential oil showed cytotoxic activity against HT29 (human colon adenocarcinoma cells), with growth inhibition of 100 and 56% (± 3). The free radical scavenging ability of the oil was assessed by the DPPH assay to show antiradical activity with IC50 of 10.4 μg/mL. TLC-bioautographic assay was used to identify the acetylcholinesterase inhibitory effect, and ascaridole was isolated and characterized (ESIMS, 1H NMR, 13C NMR and HMBC) as the responsible constituent for anticholinesterase activity.
Publikation

Bobach, C.; Tennstedt, S.; Palberg, K.; Denkert, A.; Brandt, W.; de Meijere, A.; Seliger, B.; Wessjohann, L. A.; Screening of synthetic and natural product databases: Identification of novel androgens and antiandrogens Eur. J. Med. Chem. 90, 267-279, (2015) DOI: 10.1016/j.ejmech.2014.11.026

The androgen receptor is an important pharmaceutical target for a variety of diseases. This paper presents an in silico/in vitro screening procedure to identify new androgen receptor ligands. The two-step virtual screening procedure uses a three-dimensional pharmacophore model and a docking/scoring routine. About 39,000 filtered compounds were docked with PLANTS and scored by Chemplp. Subsequent to virtual screening, 94 compounds, including 28 steroidal and 66 nonsteroidal compounds, were tested by an androgen receptor fluorescence polarization ligand displacement assay. As a result, 30 compounds were identified that show a relative binding affinity of more than 50% in comparison to 100 nM dihydrotestosterone and were classified as androgen receptor binders. For 11 androgen receptor binders of interest IC50 and Ki values were determined. The compound with the highest affinity exhibits a Ki value of 10.8 nM. Subsequent testing of the 11 compounds in a PC-3 and LNCaP multi readout proliferation assay provides insights into the potential mode of action. Further steroid receptor ligand displacement assays and docking studies on estrogen receptors α and β, glucocorticoid receptor, and progesterone receptor gave information about the specificity of the 11 most active compounds.
Publikation

Bobach, C.; Schurwanz, J.; Franke, K.; Denkert, A.; Sung, T. V.; Kuster, R.; Mutiso, P. C.; Seliger, B.; Wessjohann, L. A.; Multiple readout assay for hormonal (androgenic and antiandrogenic) and cytotoxic activity of plant and fungal extracts based on differential prostate cancer cell line behavior J. Ethnopharmacol. 155, 721-730, (2014) DOI: 10.1016/j.jep.2014.06.008

Ethnopharmacological relevanceProstate cancer is one of the most diagnosed forms of cancer among men in western regions. Many traditional applications or phytotherapeutic concepts propose to inhibit the proliferation of prostate cancer cells. In order to detect influences of plant or fungal extracts and derived fractions on androgen receptor signaling pathways, a differentiating cell proliferation assay was established, which enables the simultaneous detection of hormonal and cytotoxic effects.Material and methodsThe well characterized prostate cancer cell lines LNCaP and PC-3 were used in a multiple readout assay. In all, 186 fractions of 23 traditionally used organisms were screened regarding their effects on proliferation of the two prostate cancer cell lines. The fractions were prepared by accelerated solvent extraction followed by gradient extrography. Extracts of the potential hormonally active plants Cibotium barometz, Heteropterys chrysophylla, and Sideroxylon obtusifolium (= Bumelia sartorum) were phytochemically investigated.ResultsFractions from Cibotium barometz, Cortinarius rubellus, Cyrtomium falcatum, Heteropterys chrysophylla, Nephrolepis exaltata, Salvia miltiorrhiza, Sideroxylon obtusifolium, Trichilia emetica, and Trimeria grandifolia exhibited hormonal influences on prostate cancer cells. Cytotoxic activity towards human cell lines was detected for the first time for fractions from Aglaia spectabilis (A. gigantea), Nephrolepis exaltata and Cortinarius brunneus.ConclusionsThe differential behavior of the two prostate cancer cell lines allows the discrimination between potential androgenic or antiandrogenic activities and effects on the estrogen or glucocorticoid receptor as well as cytotoxic activities. The combined cell lines assay can help to assess the biological activities of material used in traditional medicine.
Publikation

Ali, N. A. A.; Wurster, M.; Denkert, A.; Al-Sokari, S. S.; Lindequist, U.; Wessjohann, L.; Cytotoxic and antiphytofungal activity of the essential oils from two artemisia species World J. Pharm. Res. 3, 1350-1354, (2014)

Hydrodistilled essential oils from aerial parts of Artemisia abyssinica Sch.Bip. ex A. Rich, and Artemisia arborescens L. growing in Yemen were screened for their cytotoxic and antiphytofungal properties as well as their chemical compositions. Twenty-seven components were identified in the essential oils and the main components of these species were found to be davanone (42.34%), camphor (22.88%), nerolidol (8.96%), and chamazulene (4.46%), from A. abyssinica oil and artemisia ketone (51.05%), camphor (14.09%), α-bisabolol (12.56%) and α-phellandrene (8.69%) from A. arborescens. At concentration of 50 and 25 μg/mL, A. arborescens oil showed a strong cytotoxic activity with growth inhibition of 95%(±1.6) and 74%(±3.8) (IC50 of 16.91 μg/mL) against HT29 tumor cells (Human colonic adenocarcinoma cells), while A. abyssinica oil exhibited at concentration of 100 and 50 μg/mL growth inhibition of 71.0% (±12.5) and 27.3%(±14.4) (IC50 of 75.42 μg/mL) respectively. Bioautographic assay was used to evaluate the antiphytofungal activity of the oils against Cladosporium cucumerinum.
Publikation

Ali, N. A. A.; Al-Fatimi, M. A.; Crouch, R. A.; Denkert, A.; Setzer, W. N.; Wessjohann, L.; Antimicrobial, Antioxidant, and Cytotoxic Activities of the Essential Oil of Tarchonanthus camphoratus Nat. Prod. Commun. 8, 683-686, (2013) DOI: 10.1177/1934578X1300800534

The leaf essential oil of Tarchonanthuscamphoratus(Asteraceae) was obtained by hydrodistillation and analyzed by GC-MS. Fifty-six components were characterized, representing 94.2% of the total oil with oxygenated monoterpenes (48.3%) and oxygenated sesquiterpenes (32.7%) as the major groups. The principal constituents were identified as endo-fenchol (21.2%), trans-pinene hydrate (8.8%), caryophyllene oxide (7.5%), α-terpineol (6.4%), τ-cadinol (6.4%), and α-cadinol (5.2%). The essential oil was evaluated for its antimicrobial activity using a disc diffusion assay resulting in the moderate inhibition of a number of common human pathogenic bacteria, including methicillin-resistant Staphylococcus aureus(MRSA) and the yeast Candida albicans. The inhibition zones varied from 10 to 14mm/disc. Furthermore, the antioxidant capacity of the essential oil was examined using an in vitroradical scavenging activity test. The T. camphoratus essential oil scavenged 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), resulting in an IC50value of 5.6 mg/mL. At concentrations of 100 and 50μg/mL, the oil showed cytotoxic activity, with growth inhibition of 59.1% (±4.2), and 16.2% (±8.7) against HT29 tumor cells (human colonic adenocarcinoma cells), respectively(IC50 = 84.7 ± 7.5 μg/mL).
Publikation

Ali, N. A. A.; Wurster, M.; Denkert, A.; Arnold, N.; Fadail, I.; Al-Didamony, G.; Lindequist, U.; Wessjohann, L.; Setzer, W. N.; Chemical Composition, Antimicrobial, Antioxidant and Cytotoxic Activity of Essential Oils of Plectranthus cylindraceus and Meriandra benghalensis from Yemen Nat. Prod. Commun. 7, 1099-1102, (2012) DOI: 10.1177/1934578X1200700834

The chemical composition, antimicrobial, antioxidant and cytotoxic activities of the essential oils isolated from the leaves of Plectranthus cylindraceus Hoechst. ex. Benth. (EOPC) and Meriandra benghalensis (Roxb.) Benth. (EOMB) were investigated. Sixteen compounds were identified in P. cylindraceus oil representing 94.5% of the oil content with thymol (68.5%), terpinolene (5.3%), β-selinene (4.7%), β-caryophyllene (4.0%), δ-cadinol (2.1%), and ar-curcumene (1.7%) as the major compounds. In M. benghalensis oil, 12 compounds were identified, which made up 82.0% of the total oil. The most abundant constituents were camphor (43.6%), 1,8-cineole (10.7%), α-eudesmol (5.8%), caryophyllene oxide (5.8%), camphene (5.3%) and borneol (3.4%). The antimicrobial activities of both oils were evaluated against five microorganisms with the disc diffusion test, the broth micro-dilution method and a semiquantitative bioautographic test. The most sensitive microorganisms for P. cylindraceus oil were S. aureus, B. subtilis, and C. albicans with inhibition zones of 38, 42, and 43 mm and MIC values of 0.39, 0.18, and, 0.18 μL/mL, respectively. M. benghalensis oil showed weak to moderate activity against the tested microorganisms. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay was employed to study the potential antioxidant activities of both oils. The antioxidant activity of P. cylindraceus oil (IC50 34.5 μg/mL) appeared to be higher than that of M. benghalensis oil (IC50 935 μg/mL). At a concentration of 100 μg/mL, EOMB showed a stronger cytotoxic activity, with growth inhibition of 71% against HT29 tumor cells, than EOPC (18%).
Publikation

Pando, O.; Stark, S.; Denkert, A.; Porzel, A.; Preusentanz, R.; Wessjohann, L. A.; The Multiple Multicomponent Approach to Natural Product Mimics: Tubugis, N-Substituted Anticancer Peptides with Picomolar Activity J. Am. Chem. Soc. 133, 7692-7695, (2011) DOI: 10.1021/ja2022027

The synthesis of a new generation of highly cytotoxic tubulysin analogues (i.e., tubugis) is described. In the key step, the rare, unstable, and synthetically difficult to introduce tertiary amide–N,O-acetal moiety required for high potency in natural tubulysins is replaced by a dipeptoid element formed in an Ugi four-component reaction. Two of the four components required are themselves produced by other multicomponent reactions (MCRs). Thus, the tubugis represent the first examples of the synthesis of natural-product-inspired compounds using three intertwined isonitrile MCRs.
Publikation

Shabaan, S.; Ba, L. A.; Abbas, M.; Burkholz, T.; Denkert, A.; Gohr, A.; Wessjohann, L. A.; Sasse, F.; Weber, W.; Jacob, C.; Multicomponent reactions for the synthesis of multifunctional agents with activity against cancer cells Chem. Commun. 4702, (2009) DOI: 10.1039/B823149D

Multicomponent Passerini and Ugi reactions enable the fast and efficient synthesis of redox-active multifunctional selenium and tellurium compounds, of which some show considerable cytotoxicity against specific cancer cells.
Publikation

Pando, O.; Dörner, S.; Preusentanz, R.; Denkert, A.; Porzel, A.; Richter, W.; Wessjohann, L.; First Total Synthesis of Tubulysin B Org. Lett. 11, 5567-5569, (2009) DOI: 10.1021/ol902320w

The first total synthesis of tubulysin B is described. The aziridine route to tubuphenylalanine (Tup) of the tubulysin D/U-series could not be transferred to the synthesis of tubutyrosine (blue moiety). Therefore, tubutyrosine (Tut) was synthesized by a Wittig olefination/diastereoselective catalytic reduction sequence. Interestingly, the C-2 epimer of tubulysin B has a cytotoxic activity almost identical to the natural diastereomer.
  • Die Leibniz-Gemeinschaft
  • Digitalisierung in der Landwirtschaft
  • Martin-Luther Universität Halle
IPB Mainnav Search