| 1. |
- Deyou, Tsegaye, et al.
(author)
-
Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp teitensis
- 2017
-
In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:7, s. 2060-2066
-
Journal article (peer-reviewed)abstract
- A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A-D (2-5), along with nine known compounds (6-14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 mu M, respectively.
|
|
| 2. |
- Deyou, Tsegaye, et al.
(author)
-
Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis
- 2015
-
In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025 .- 0974-5211. ; 78:12, s. 2932-2939
-
Journal article (peer-reviewed)abstract
- Five new compounds, 4-O-geranylisoliquiritigenin (1), 12-dihydrousararotenoid B (2), 12-dihydrousararotenoid C (3), 4'-O-geranyl-7-hydroxyflavanone (4), and 4'O-geranyl-7-hydroxydihydroflavanol (5), along with 12 known natural products (6-17) were isolated from the CH2Cl2/MeOH (1:1) extract of the root bark of Millettia usaramensis ssp. usaramensis by chromatographic separation. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas their absolute configurations were established on the basis of chiroptical data and in some cases also by X-ray crystallography. The crude extract was moderately active (IC50 = 11.63 mu g/mL) against the ER-negative MDB-MB-231 human breast cancer cell line, and accordingly compounds 6, 8, 9, 10, 12, and 16 also showed moderate to low cytotoxic activities (IC50 25.7-207.2 mu M). The new natural product 1 exhibited antiplasmodial activity with IC50 values of 3.7 and 5.3 mu M against the chloroquine-sensitive 3D7 and the chloroquine-resistant Dd2 Plasmodium falciparum strains, respectively, and was also cytotoxic to the HEK293 cell line.
|
|
| 3. |
- Esbjörner Winters, Elin, 1978, et al.
(author)
-
Direct Observations of Amyloid beta Self-Assembly in Live Cells Provide Insights into Differences in the Kinetics of A beta(1-40) and A beta(1-42) Aggregation
- 2014
-
In: Chemistry and Biology. - : Elsevier BV. - 1074-5521. ; 21:6, s. 732-742
-
Journal article (peer-reviewed)abstract
- Insight into how amyloid beta (A beta) aggregation occurs in vivo is vital for understanding the molecular pathways that underlie Alzheimer's disease and requires new techniques that provide detailed kinetic and mechanistic information. Using noninvasive fluorescence lifetime recordings, we imaged the formation of A beta(1-40) and A beta(1-42) aggregates in live cells. For both peptides, the cellular uptake via endocytosis is rapid and spontaneous. They are then retained in lysosomes, where their accumulation leads to aggregation. The kinetics of A beta(1-42) aggregation are considerably faster than those of A beta(1-40) and, unlike those of the latter peptide, show no detectable lag phase. We used superresolution fluorescence imaging to examine the resulting aggregates and could observe compact amyloid structures, likely because of spatial confinement within cellular compartments. Taken together, these findings provide clues as to how A beta aggregation may occur within neurons.
|
|
| 4. |
- Nyandoro, Stephen S., 1975, et al.
(author)
-
A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii
- 2019
-
In: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 24:15
-
Journal article (peer-reviewed)abstract
- Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2-13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 mu g/mL. The isolated metabolites dichamanetin, (E)-acetylmelodorinol, and cleistenolide showed IC50 = 9.3, 7.6 and 15.2 mu M, respectively, against P. falciparum 3D7. Both the crude extract and the isolated compounds exhibited cytotoxicity against the triple-negative, aggressive breast cancer cell line, MDA-MB-231, with IC50 = 42.0 mu g/mL (crude extract) and 9.6-30.7 mu M (isolated compounds). Our findings demonstrate the potential applicability of C. kirkii as a source of antimalarial and anticancer agents.
|
|
| 5. |
- Nyandoro, Stephen S., 1975, et al.
(author)
-
Flavonoids from Erythrina schliebenii
- 2017
-
In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:2, s. 377-383
-
Journal article (peer-reviewed)abstract
- Prenylated and O-methylflavonoids including one new pterocarpan (1), three new isoflavones (2-4), and nineteen known natural products (5-23) were isolated and identified from the root, stem bark, and leaf extracts of Erythrina schliebenii. The crude extracts and their constituents were evaluated for antitubercular activity against Mycobacterium tuberculosis (H37Rv strain), showing MICs of 32-64 mu g mL(-1) and 36.9-101.8 mu M, respectively. Evaluation of their toxicity against the aggressive human breast cancer cell line MDA-MB-231 indicated EC50 values of 13.0-290.6 mu M (pure compounds) and 38.3 to >100 mu g mL(-1) (crude extracts). RAMSON D, 1973, PHYTOCHEMISTRY, V12, P2211
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Abdissa, Negera, et al.
(author)
-
Naphthalene Derivatives from the Roots of Pentas parvifolia and Pentas bussei
- 2016
-
In: Journal of natural products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 79:9, s. 2181-2187
-
Journal article (peer-reviewed)abstract
- The phytochemical investigation of the CH2Cl2/MeOH (1:1) extract of the roots of Pentas parvifolia led to the isolation of three new naphthalenes, parvinaphthols A (1), B (2), and C (3), two known anthraquinones, and five known naphthalene derivatives. Similar investigation of the roots of Pentas bussei afforded a new polycyclic naphthalene, busseihydroquinone E (4), a new 2,2′-binaphthralenyl-1,1′-dione, busseihydroquinone F (5), and five known naphthalenes. All purified metabolites were characterized by NMR and MS data analyses, whereas the absolute configurations of 3 and 4 were determined by single-crystal X-ray diffraction studies. The E-geometry of compound 5 was supported by DFT-based chemical shift calculations. Compounds 2-4 showed marginal cytotoxicity against the MDA-MB-231 human triple-negative breast cancer cell line with IC50 values ranging from 62.3 to 129.6 μM. © 2016 The American Chemical Society and American Society of Pharmacognosy.
|
|
| 9. |
|
|
| 10. |
- Brath, Ulrika, et al.
(author)
-
Paramagnetic ligand tagging to identify protein binding sites
- 2015
-
In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 137:35, s. 11391-11398
-
Journal article (peer-reviewed)abstract
- Transient biomolecular interactions are the cornerstones of the cellular machinery. The identification of the binding sites for low affinity molecular encounters is essential for the development of high affinity pharmaceuticals from weakly binding leads but is hindered by the lack of robust methodologies for characterization of weakly binding complexes. We introduce a paramagnetic ligand tagging approach that enables localization of low affinity protein–ligand binding clefts by detection and analysis of intermolecular protein NMR pseudocontact shifts, which are invoked by the covalent attachment of a paramagnetic lanthanoid chelating tag to the ligand of interest. The methodology is corroborated by identification of the low millimolar volatile anesthetic interaction site of the calcium sensor protein calmodulin. It presents an efficient route to binding site localization for low affinity complexes and is applicable to rapid screening of protein–ligand systems with varying binding affinity.
|
|
