TY  - JOUR
A1  - Abdissa, Negera
A1  - Heydenreich, Matthias
A1  - Midiwo, Jacob O.
A1  - Ndakala, Albert
A1  - Majer, Zsuzsanna
A1  - Neumann, Beate
A1  - Stammler, Hans-Georg
A1  - Sewald, Norbert
A1  - Yenesew, Abiy
T1  - A xanthone and a phenylanthraquinone from the roots of Bulbine frutescens, and the revision of six seco-anthraquinones into xanthones
JF  - Phytochemistry letters
N2  - Phytochemical investigation of the dichloromethane/methanol (1:1) extract of the roots of Bulbine frutescens led to the isolation of a new xanthone, 8-hydroxy-6-methylxanthone-1-carboxylic acid (1) and a new phenylanthraquinone, 6',8-O-dimethylknipholone (2) along with six known compounds. The structures were elucidated on the basis of NMR and MS spectral data analyses. The structure of compound 1 was confirmed through X-ray crystallography which was then used as a reference to propose the revision of the structures of six seco-anthraquinones into xanthones. The isolated compounds were evaluated for cytotoxicity against human cervix carcinoma KB-3-1 cells with the phenylanthraquinone knipholone being the most active (IC50 = 0.43 mu M). Two semi-synthetic knipholone derivatives, knipholone Mannich base and knipholone-1,3-oxazine, were prepared and tested for cytotoxic activity; both showed moderate activities (IC50 value of 1.89 and 2.50 mu M, respectively). (C) 2014 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
KW  - Bulbine frutescens
KW  - Xanthone
KW  - seco-Anthraquinone
KW  - Phenylanthraquinone
KW  - Cytotoxicity
KW  - Structure revision
Y1  - 2014
U6  - https://doi.org/10.1016/j.phytol.2014.04.004
SN  - 1874-3900
SN  - 1876-7486
VL  - 9
SP  - 67
EP  - 73
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Abdissa, Negera
A1  - Induli, Martha
A1  - Akala, Hoseah M.
A1  - Heydenreich, Matthias
A1  - Midiwo, Jacob O.
A1  - Ndakala, Albert
A1  - Yenesew, Abiy
T1  - Knipholone cyclooxanthrone and an anthraquinone dimer with antiplasmodial activities from the roots of Kniphofia foliosa
JF  - Phytochemistry letters
N2  - A new phenylanthrone, named knipholone cyclooxanthrone and a dimeric anthraquinone, 10-methoxy-10,7'-(chrysophanol anthrone)-chrysophanol were isolated from the roots of Kniphofia foliosa together with the rare naphthalene glycoside, dianellin. The structures were determined by NMR and mass spectroscopic techniques. The compounds showed antiplasmodial activities against the chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum with 10-methoxy-10,7'-(chrysophanol anthrone)-chrysophanol being the most active with IC50 values of 1.17 +/- 0.12 and 4.07 +/- 1.54 mu g/ml, respectively.
KW  - Kniphofia foliosa
KW  - Asphodelaceae
KW  - Roots
KW  - Anthraquinone
KW  - Knipholone cyclooxanthrone
KW  - 10-Methoxy-10,7 '-(chrysophanol anthrone)-chrysophanol
KW  - Dianellin
KW  - Malaria
Y1  - 2013
U6  - https://doi.org/10.1016/j.phytol.2013.02.005
SN  - 1874-3900
VL  - 6
IS  - 2
SP  - 241
EP  - 245
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Adem, Fozia A.
A1  - Mbaveng, Armelle T.
A1  - Kuete, Victor
A1  - Heydenreich, Matthias
A1  - Ndakala, Albert
A1  - Irungu, Beatrice
A1  - Yenesew, Abiy
A1  - Efferth, Thomas
T1  - Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer
JF  - Phytomedicine : international journal of phytotherapy and phytopharmacology
N2  - Background: While incidences of cancer are continuously increasing, drug resistance of malignant cells is observed towards almost all pharmaceuticals. Several isoflavonoids and flavonoids are known for their cytotoxicity towards various cancer cells. Methods: The cytotoxicity of compounds was determined based on the resazurin reduction assay. Caspases activation was evaluated using the caspase-Glo assay. Flow cytometry was used to analyze the cell cycle (propodium iodide (PI) staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). CCRF-CEM leukemia cells were used as model cells for mechanistic studies. Results: Compounds 1, 2 and 4 displayed IC50 values below 20 mu M towards CCRF-CEM and CEM/ADR5000 leukemia cells, and were further tested towards a panel of 7 carcinoma cells. The IC50 values of the compounds against carcinoma cells varied from 16.90 mu M (in resistant U87MG.Delta EGFR glioblastoma cells) to 48.67 mu M (against HepG2 hepatocarcinoma cells) for 1, from 7.85 mu M (in U87MG.Delta EGFR cells) to 14.44 mu M (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2, from 4.96 mu M (towards U87MG.Delta EGFRcells) to 7.76 mu M (against MDA-MB231/BCRP cells) for 4, and from 0.07 mu M (against MDA-MB231 cells) to 2.15 mu M (against HepG2 cells) for doxorubicin. Compounds 2 and 4 induced apoptosis in CCRF-CEM cells mediated by MMP alteration and increased ROS production. Conclusion: The present report indicates that isoflavones and biflavonoids from Ormocarpum kirkii are cytotoxic compounds with the potential of being exploited in cancer chemotherapy. Compounds 2 and 4 deserve further studies to develop new anticancer drugs to fight sensitive and resistant cancer cell lines.
KW  - Apoptosis
KW  - Cancer
KW  - Ormocarpum kirkii
KW  - Isoflavone
KW  - Biflavonoid
KW  - Multi-drug resistance
Y1  - 2019
U6  - https://doi.org/10.1016/j.phymed.2019.152853
SN  - 0944-7113
SN  - 1618-095X
VL  - 58
PB  - Elsevier
CY  - München
ER  - 
TY  - JOUR
A1  - Akampurira, Denis
A1  - Akala, Hoseah M.
A1  - Derese, Solomon
A1  - Heydenreich, Matthias
A1  - Yenesew, Abiy
T1  - A new C-C linked benzophenathridine-2-quinoline dimer, and the antiplasmodial activity of alkaloids from Zanthoxylum holstzianum
JF  - Natural product research
N2  - The CH2Cl2/MeOH (1:1) extract of Zanthoxylum holstzianum stem bark showed good antiplasmodial activity (IC50 2.5 +/- 0.3 and 2.6 +/- 0.3 mu g/mL against the W2 and D6 strains of Plasmodium falciparum, respectively). From the extract five benzophenanthridine alkaloids [8-acetonyldihydrochelerythrine (1), nitidine (2), dihydrochelerythine (3), norchelerythrine (5), arnottianamide (8)]; a 2-quinolone alkaloid [N-methylflindersine (4)]; a lignan [4,4 '-dihydroxy-3,3 '-dimethoxylignan-9,9 '-diyl diacetate (7)] and a dimer of a benzophenanthridine and 2-quinoline [holstzianoquinoline (6)] were isolated. The CH2Cl2/MeOH (1:1) extract of the root bark afforded 1, 3-6, 8, chelerythridimerine (9) and 9-demethyloxychelerythrine (10). Holstzianoquinoline (6) is new, and is the second dimer linked by a C-C bond of a benzophenanthridine and a 2-quinoline reported thus far. The compounds were identified based on spectroscopic evidence. Amongst five compounds (1-5) tested against two strains of P. falciparum, nitidine (IC50 0.11 +/- 0.01 mu g/mL against W2 and D6 strains) and norchelerythrine (IC50 value of 0.15 +/- 0.01 mu g/mL against D6 strain) were the most active.
KW  - Antiplasmodial
KW  - benzophenanthridine alkaloid
KW  - holstzianoquinoline;
KW  - rutaceae
KW  - Zanthoxylum holstzianum
Y1  - 2022
U6  - https://doi.org/10.1080/14786419.2022.2034810
SN  - 1478-6419
SN  - 1478-6427
VL  - 37
IS  - 13
SP  - 2161
EP  - 2171
PB  - Taylor & Francis
CY  - London [u.a.]
ER  - 
TY  - JOUR
A1  - Andayi, Andrew W.
A1  - Yenesew, Abiy
A1  - Derese, Solomon
A1  - Midiwo, Jacob O.
A1  - Gitu, Peter M.
A1  - Jondiko, Ogoche J. I.
A1  - Akala, Hoseah M.
A1  - Liyala, Pamela
A1  - Wangui, Julia
A1  - Waters, Norman C.
A1  - Heydenreich, Matthias
A1  - Peter, Martin G.
T1  - Antiplasmodial flavonoids from Erythrina sacleuxii
N2  - The acetone extracts of the root bark and stem bark of Erythrina sacleuxii showed antiplasmodial activities against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Chromatographic separation of the acetone extract of the root bark afforded a new isoflavone, 7-hydroxy-4 -methoxy-3'- prenylisoflavone (trivial name 5-deoxy-3' - prenylbiochanin A) along with known isoflavonoids as the antiplasmodial principles. Flavonoids and isoflavonoids isolated from the stem bark of E. sucleuxii were also tested and showed antiplasmodial activities. The structures were determined on the basis of spectroscopic evidence
Y1  - 2006
UR  - http://www.thieme-connect.com/ejournals/toc/plantamedica
U6  - https://doi.org/10.1055/s-2005-873200
SN  - 0032-0943
ER  - 
TY  - JOUR
A1  - Arias, Hugo R.
A1  - Feuerbach, Dominik
A1  - Schmidt, Bernd
A1  - Heydenreich, Matthias
A1  - Paz, Cristian
A1  - Ortells, Marcelo O.
T1  - Drimane Sesquiterpenoids Noncompetitively Inhibit Human alpha 4 beta 2 Nicotinic Acetylcholine Receptors with Higher Potency Compared to Human alpha 3 beta 4 and alpha 7 Subtypes
JF  - Journal of natural products
N2  - The drimane sesquiterpenoids drimenin, cinnamolide, dendocarbin A, and polygodial were purified from the Canelo tree (Drimys winteri) and chemically characterized by spectroscopic methods. The pharmacological activity of these natural compounds were determined on hα4β2, hα3β4, and hα7 nicotinic acetylcholine receptors (AChRs) by Ca2+ influx measurements. The results established that drimane sesquiterpenoids inhibit AChRs with the following selectivity: hα4β2 > hα3β4 > hα7. In the case of hα4β2 AChRs, the following potency rank order was determined (IC50’s in μM): drimenin (0.97 ± 0.35) > cinnamolide (1.57 ± 0.36) > polygodial (62.5 ± 19.9) ≫ dendocarbin A (no activity). To determine putative structural features underlying the differences in inhibitory potency at hα4β2 AChRs, additional structure–activity relationship and molecular docking experiments were performed. The Ca2+ influx and structural results supported a noncompetitive mechanism of inhibition, where drimenin interacted with luminal and nonluminal (TMD-β2 intrasubunit) sites. The structure–activity relationship results, i.e., the lower the ligand polarity, the higher the inhibitory potency, supported the nonluminal interaction. Ligand binding to both sites might inhibit the hα4β2 AChR by a cooperative mechanism, as shown experimentally (nH > 1). Drimenin could be used as a molecular scaffold for the development of more potent inhibitors with higher selectivity for the hα4β2 AChR.
Y1  - 2018
U6  - https://doi.org/10.1021/acs.jnatprod.7b00893
SN  - 0163-3864
SN  - 1520-6025
VL  - 81
IS  - 4
SP  - 811
EP  - 817
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Atilaw, Yoseph
A1  - Duffy, Sandra
A1  - Heydenreich, Matthias
A1  - Muiva-Mutisya, Lois
A1  - Avery, Vicky M.
A1  - Erdelyi, Mate
A1  - Yenesew, Abiy
T1  - Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata
JF  - Molecules
N2  - In our search for new antiplasmodial agents, the CH2Cl2/CH3OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL concentration. From this extract three new chalconoids, E-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (1, aequichalcone A), Z-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (2, aequichalcone B), 4-ethoxy-3-hydroxypraecansone B (3, aequichalcone C) and a new pterocarpene, 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (4), along with seven known compounds were isolated. The purified compounds were characterized by NMR spectroscopic and mass spectrometric analyses. Compound 1 slowly converts into 2 in solution, and thus the latter may have been enriched, or formed, during the extraction and separation process. The isomeric compounds 1 and 2 were both observed in the crude extract. Some of the isolated constituents showed good to moderate antiplasmodial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.
KW  - Tephrosia aequilata
KW  - chalcone
KW  - retrochalcone
KW  - aequichalcone A
KW  - aequichalcone B
KW  - aequichalcone C
KW  - pterocarpene
KW  - antiplasmodial
Y1  - 2017
U6  - https://doi.org/10.3390/molecules22020318
SN  - 1420-3049
VL  - 22
IS  - 2
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Atilaw, Yoseph
A1  - Heydenreich, Matthias
A1  - Ndakala, Albert
A1  - Akala, Hoseah M.
A1  - Kamau, Edwin
A1  - Yenesew, Abiy
T1  - 3-Oxo-14 alpha, 15 alpha-epoxyschizozygine: A new schizozygane indoline alkaloid from Schizozygia coffaeoides
JF  - Phytochemistry letters
N2  - The stem bark extract of Schizozygia coffaeoides (Apocynaceae) showed moderate antiplasmodial activity (IC50 = 8-12 mu g/mL) against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Chromatographic separation of the extract led to the isolation of a new schizozygane indoline alkaloid, named 3-oxo-14 alpha, 15 alpha-epoxyschizozygine. In addition, two dimeric anthraquinones, cassiamin A and cassiamin B, were identified for the first time in the family Apocynaceae. The structures of the isolated compounds were deduced on the basis of spectroscopic evidence. The schizozygane indole alkaloids showed good to moderate antiplasmodial activities (IC50 = 13-52 mu m). (C) 2014 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
KW  - Schizozygia coffaeoides
KW  - Schizozygane indoline alkaloid
KW  - 3-Oxo-14 alpha, 15 alpha-epoxyschizozygine
KW  - Dimeric anthraquinone
KW  - Cassiamin A
KW  - Cassiamin B
Y1  - 2014
U6  - https://doi.org/10.1016/j.phytol.2014.07.003
SN  - 1874-3900
SN  - 1876-7486
VL  - 10
SP  - 28
EP  - 31
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Baraza, Lilechi D.
A1  - Neser, Wekesa
A1  - Jackson, Korir Cheruiyot
A1  - Fredrick, Juma B.
A1  - Dennis, Ochieno
A1  - Wairimu, Kamau R.
A1  - Keya, Aggrey Osogo
A1  - Heydenreich, Matthias
T1  - Antimicrobial Coumarins from the Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), from Kenya
JF  - International journal of medicinal mushrooms
N2  - Pleurotus ostreatus has been widely used as food because of its nutritional and medicinal properties. These have been attributed to the presence of macronutrients, minerals, vitamins, and amino acids, among other secondary metabolites. There are, however, few reports on the antimicrobial activities of different classes of purified compounds from P. ostreatus. This led to the current study, the objective of which was to chemically characterize the antibiotic activities of P. ()streams against selected human pathogenic bacteria and endophytic fungi. Chemical structures were determined using spectroscopic methods and by comparison with values of related structures reported in the literature. Pure compounds from P. ostreatus were tested in vitro against pathogenic bacteria (Staphylococcus aureus and Escherichia coli) and endophytic fungi (Pencillium digitatum and Fusarium prolferatum). A new compound, (E)-5,7-dimethoxy-6-(3-methylbuta-1,3-dienyl)-2H-chromen-2-one (5-methoxy-(E)-suberodiene) (compound 2), along with ergosterol (compound I.) and 5,7-dimethoxy-6-(3-methylbut-2-enyl)-2H-chromen-2-one (toddaculin; compound 3), were isolated from the fruiting bodies of P. ostreatus. The growth of S. aureus,E proliferatum, and P. digitatum colonies was inhibited in media containing compound 2, with minimum inhibitory concentrations closely comparable to those of conventional antibiotics.
KW  - Escherichia coli
KW  - Fusarium proliferatum
KW  - medicinal mushrooms
KW  - Penicillium digitatum
KW  - Pleurotus ostreatus
KW  - Staphylococcus aureus
Y1  - 2016
U6  - https://doi.org/10.1615/IntJMedMushrooms.v18.i10.60
SN  - 1521-9437
SN  - 1940-4344
VL  - 18
SP  - 905
EP  - 913
PB  - Begell House
CY  - Danbury
ER  - 
TY  - JOUR
A1  - Barta, Petra
A1  - Szatmari, Istvan
A1  - Fueloep, Ferenc
A1  - Heydenreich, Matthias
A1  - Koch, Andreas
A1  - Kleinpeter, Erich
T1  - Synthesis and stereochemistry of new naphth[1,3]oxazino[3,2-a] benzazepine and naphth[1,3]oxazino[3,2-e]thienopyridine derivatives
JF  - Tetrahedron
N2  - Through the reactions of 1- or 2-naphthol and 4,5-dihydro-3H-benz[c]azepine or 6,7-dihydrothieno[3,2-c]pyridine, new aminonaphthol derivatives were prepared. The syntheses were extended by using N-containing naphthol analogues such as 5-hydroxyisoquinoline and 6-hydroxyquinoline. The ring closures of the novel bifunctional compounds were also achieved, resulting in new naphth[2,1-e][1,3]oxazines, naphth[1,2-e][1,3]oxazines, isoquinolino[5,6-e][1,3]oxazines and quinolino[5,6-e][1,3]oxazines. H-1 NMR spectra of the target heterocycles 16, 20 and 21 were sufficiently resolved to indentify the present stereochemistry; therefore, beside computed structures, spatial experimental (dipolar coupling-NOE) and computed (ring current effect of the naphthyl moiety-TSNMRS) NMR studies were employed. The studied heterocycles exist exclusively as S(14b),R(N), R(14b),S(N), and S(16b)S(N) isomers, respectively. The flexible moieties of the studied compounds prefer. (C) 2016 Elsevier Ltd. All rights reserved.
KW  - Modified Mannich reaction
KW  - Thienopyridine
KW  - Benzazepine
KW  - NMR spectroscopy
KW  - Stereochemistry
KW  - Theoretical calculations
Y1  - 2016
U6  - https://doi.org/10.1016/j.tet.2016.03.058
SN  - 0040-4020
VL  - 72
SP  - 2402
EP  - 2410
PB  - Elsevier
CY  - Oxford
ER  -