@article{MarcoDeyouGruhonjicetal.2017, author = {Marco, Makungu and Deyou, Tsegaye and Gruhonjic, Amra and Holleran, John and Duffy, Sandra and Heydenreich, Matthias and Firtzpatrick, Paul A. and Landberg, Goran and Koch, Andreas and Derese, Solomon and Pelletier, Jerry and Avery, Vicky M. and Erdelyi, Mate and Yenesew, Abiy}, title = {Pterocarpans and isoflavones from the root bark of Millettia micans and of Millettia dura}, series = {Phytochemistry letters}, volume = {21}, journal = {Phytochemistry letters}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1874-3900}, doi = {10.1016/j.phytol.2017.07.012}, pages = {216 -- 220}, year = {2017}, language = {en} } @article{AtilawDuffyHeydenreichetal.2017, author = {Atilaw, Yoseph and Duffy, Sandra and Heydenreich, Matthias and Muiva-Mutisya, Lois and Avery, Vicky M. and Erdelyi, Mate and Yenesew, Abiy}, title = {Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata}, series = {Molecules}, volume = {22}, journal = {Molecules}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {1420-3049}, doi = {10.3390/molecules22020318}, pages = {11}, year = {2017}, abstract = {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.}, language = {en} } @article{SelemaniNondoMoshietal.2017, author = {Selemani, Ramadhani Selemani Omari and Nondo, Omari and Moshi, Mainen Julius and Erasto, Paul and Masimba, Pax Jessey and Machumi, Francis and Kidukuli, Abdul Waziri and Heydenreich, Matthias and Zofou, Denis}, title = {Anti-plasmodial activity of Norcaesalpin D and extracts of four medicinal plants used traditionally for treatment of malaria}, series = {BMC Complementary and Alternative Medicine volume}, volume = {17}, journal = {BMC Complementary and Alternative Medicine volume}, publisher = {BioMed Central}, address = {London}, issn = {1472-6882}, doi = {10.1186/s12906-017-1673-8}, pages = {8}, year = {2017}, abstract = {Background: Malaria is an old life-threatening parasitic disease that is still affecting many people, mainly children living in sub-Saharan Africa. Availability of effective antimalarial drugs played a significant role in the treatment and control of malaria. However, recent information on the emergence of P. falciparum parasites resistant to one of the artemisinin-based combination therapies suggests the need for discovery of new drug molecules. Therefore, this study aimed to evaluate the antiplasmodial activity of extracts, fractions and isolated compound from medicinal plants traditionally used in the treatment of malaria in Tanzania. Methods: Dry powdered plant materials were extracted by cold macerations using different solvents. Norcaesalpin D was isolated by column chromatography from dichloromethane root extract of Caesalpinia bonducella and its structure was assigned based on the spectral data. Crude extracts, fractions and isolated compound were evaluated for antiplasmodial activity against chloroquine-sensitive P. falciparum (3D7), chloroquine-resistant P. falciparum (Dd2, K1) and artemisinin-resistant P. falciparum (IPC 5202 Battambang, IPC 4912 Mondolkiri) strains using the parasite lactate dehydrogenase assay. Results: The results indicated that extracts of Erythrina schliebenii, Holarrhena pubescens, Dissotis melleri and C. bonducella exhibited antiplasmodial activity against Dd2 parasites. Ethanolic root extract of E. schliebenii had an IC50 of 1.87 mu g/mL while methanolic and ethanolic root extracts of H. pubescens exhibited an IC50 = 2.05 mu g/mL and IC50 = 2.43 mu g/mL, respectively. Fractions from H. pubescens and C. bonducella roots were found to be highly active against K1, Dd2 and artemisinin-resistant parasites. Norcaesalpin D from C. bonducella root extract was active with IC50 of 0.98, 1.85 and 2.13 mu g/mL against 3D7, Dd2 and IPC 4912-Mondolkiri parasites, respectively. Conclusions: Antiplasmodial activity of norcaesalpin D and extracts of E. schliebenii, H. pubescens, D. melleri and C. bonducella reported in this study requires further attention for the discovery of antimalarial lead compounds for future drug development.}, language = {en} } @article{MuthauraKerikoMutaietal.2017, author = {Muthaura, Charles N. and Keriko, Joseph M. and Mutai, Charles and Yenesew, Abiy and Heydenreich, Matthias and Atilaw, Yoseph and Gathirwa, Jeremiah W. and Irungu, Beatrice N. and Derese, Solomon}, title = {Antiplasmodial, cytotoxicity and phytochemical constituents of four maytenus species used in traditional medicine in Kenya}, series = {The natural products journal}, volume = {7}, journal = {The natural products journal}, number = {2}, publisher = {Bentham Science Publ.}, address = {Sharjah}, issn = {2210-3155}, doi = {10.2174/2210315507666161206144050}, pages = {144 -- 152}, year = {2017}, abstract = {Background: In Kenya, several species of the genus Maytenus are used in traditional medicine to treat many diseases including malaria. In this study, phytochemical constituents and extracts of Maytenus undata, M. putterlickioides, M. senegalensis and M. heterophylla were evaluated to determine compound/s responsible for antimalarial activity. Objective: To isolate antiplasmodial compounds from these plant species which could be used as marker compounds in the standardization of their extracts as a phytomedicine for malaria. Methods: Constituents were isolated through activity-guided fractionation of the MeOH/CHCl3 (1:1) extracts and in vitro inhibition of Plasmodium falciparum. Cytotoxicity was evaluated using Vero cells and the compounds were elucidated on the basis of NMR spectroscopy. Results: Fractionation of the extracts resulted in the isolation of ten known compounds. Compound 1 showed promising antiplasmodial activity with IC50, 3.63 and 3.95 ng/ml against chloroquine sensitive (D6) and resistant (W2) P. falciparum, respectively and moderate cytotoxicity (CC50, 37.5 ng/ml) against Vero E6 cells. The other compounds showed weak antiplasmodial (IC50 > 1.93 mu g/ml) and cytotoxic (CC50 > 39.52 mu g/ml) activities against P. falciparum and Vero E6 cells, respectively. Conclusion: (20 alpha)-3-hydroxy-2-oxo-24-nor-friedela-1(10),3,5,7-tetraen-carboxylic acid-(29)-methyl-ester (pristimerin) (1) was the most active marker and lead compound that warrants further investigation as a template for the development of new antimalarial drugs. Pristimerin is reported for the first time in M. putterlickioides. 3-Hydroxyolean-12-en-28-oic acid (oleanolic acid) (5), stigmast-5-en-3-ol (beta-sitosterol) (6), 3-oxo-28-friedelanoic acid (7), olean-12-en-3-ol (beta-amyrin) (8), lup-20(29)-en-3-ol (lupeol) (9) and lup-20(29)-en-3-one (lupenone) (10) are reported for the first time in M. undata.}, language = {en} } @article{DeyouMarcoHeydenreichetal.2017, author = {Deyou, Tsegaye and Marco, Makungu and Heydenreich, Matthias and Pan, Fangfang and Gruhonjic, Amra and Fitzpatrick, Paul A. and Koch, Andreas and Derese, Solomon and Pelletier, Jerry and Rissanen, Kari and Yenesew, Abiy and Erdelyi, Mate}, title = {Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp teitensis}, series = {Journal of natural products}, volume = {80}, journal = {Journal of natural products}, publisher = {American Chemical Society}, address = {Washington}, issn = {0163-3864}, doi = {10.1021/acs.jnatprod.7b00255}, pages = {2060 -- 2066}, year = {2017}, 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.}, language = {en} } @article{HildebrandHeydenreichLaschewskyetal.2017, author = {Hildebrand, Viet and Heydenreich, Matthias and Laschewsky, Andre and Moeller, Heiko M. and M{\"u}ller-Buschbaum, Peter and Papadakis, Christine M. and Schanzenbach, Dirk and Wischerhoff, Erik}, title = {"Schizophrenic" self-assembly of dual thermoresponsive block copolymers bearing a zwitterionic and a non-ionic hydrophilic block}, series = {Polymer : the international journal for the science and technology of polymers}, volume = {122}, journal = {Polymer : the international journal for the science and technology of polymers}, publisher = {Elsevier}, address = {Oxford}, issn = {0032-3861}, doi = {10.1016/j.polymer.2017.06.063}, pages = {347 -- 357}, year = {2017}, abstract = {Several series of presumed dual thermo-responsive diblock copolymers consisting of one non-ionic and one zwitterionic block were synthesized via consecutive reversible addition-fragmentation chain transfer (RAFT) polymerization. For all copolymers, poly(N-isopropylmethacrylamide) was chosen as non-ionic block that shows a coil-to-globule collapse transition of the lower critical solution temperature (LCST) type. In contrast, the chemical structure of zwitterionic blocks, which all belonged to the class of poly(sulfobetaine methacrylate)s, was varied broadly, in order to tune their coil-to-globule collapse transition of the upper critical solution temperature (UCST) type. All polymers were labeled with a solvatochromic fluorescent end-group. The dual thermo-responsive behavior and the resulting multifarious temperature-dependent self-assembly in aqueous solution were mapped by temperature resolved turbidimetry, H-1 NMR spectroscopy, dynamic light scattering (DLS), and fluorescence spectroscopy. Depending on the relative positions between the UCST-type and LCST-type transition temperatures, as well as on the width of the window in-between, all the four possible modes of stimulus induced micellization can be realized. This includes classical induced micellization due to a transition from a double hydrophilic, or respectively, from a double hydrophobic to an amphiphilic state, as well as "schizophrenic" behavior, where the core- and shell-forming blocks are inverted. The exchange of the roles of the hydrophilic and hydrophobic block in the amphiphilic states is possible through a homogeneous intermediate state or a heterogeneous one. (C) 2017 Elsevier Ltd. All rights reserved.}, language = {en} } @article{KleinpeterHeydenreichKochetal.2017, author = {Kleinpeter, Erich and Heydenreich, Matthias and Koch, Andreas and Krtitschka, Angela and Kr{\"u}ger, Tobias and Linker, Torsten}, title = {NMR spectroscopic conformational analysis of 4-methylene-cyclohexyl pivalateThe effect of sp(2) hybridization}, series = {Magnetic resonance in chemistry}, volume = {55}, journal = {Magnetic resonance in chemistry}, publisher = {Wiley}, address = {Hoboken}, issn = {0749-1581}, doi = {10.1002/mrc.4630}, pages = {1073 -- 1078}, year = {2017}, abstract = {The conformational equilibrium of the axial/equatorial conformers of 4-methylene-cyclohexyl pivalate is studied by dynamic NMR spectroscopy in a methylene chloride/freon mixture. At 153K, the ring interconversion gets slow on the nuclear magnetic resonance timescale, the conformational equilibrium (-G degrees) can be examined, and the barrier to ring interconversion (G(\#)) can be determined. The structural influence of sp(2) hybridization on both G degrees and G(\#) of the cyclohexyl moiety can be quantified.}, language = {en} }