@article{BruennertSeupelGoyaletal.2023,
  author    = {Br{\"u}nnert, Daniela and Seupel, Raina and Goyal, Pankaj and Bach, Matthias and Schraud, Heike and Kirner, Stefanie and K{\"o}ster, Eva and Feineis, Doris and Bargou, Ralf C. and Schlosser, Andreas and Bringmann, Gerhard and Chatterjee, Manik},
  title     = {Ancistrocladinium A induces apoptosis in proteasome inhibitor-resistant multiple myeloma cells: a promising therapeutic agent candidate},
  series = {Pharmaceuticals},
  volume    = {16},
  journal   = {Pharmaceuticals},
  number    = {8},
  issn      = {1424-8247},
  doi       = {10.3390/ph16081181},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362887},
  year      = {2023},
  abstract  = {The N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A belongs to a novel class of natural products with potent antiprotozoal activity. Its effects on tumor cells, however, have not yet been explored. We demonstrate the antitumor activity of ancistrocladinium A in multiple myeloma (MM), a yet incurable blood cancer that represents a model disease for adaptation to proteotoxic stress. Viability assays showed a potent apoptosis-inducing effect of ancistrocladinium A in MM cell lines, including those with proteasome inhibitor (PI) resistance, and in primary MM cells, but not in non-malignant blood cells. Concomitant treatment with the PI carfilzomib or the histone deacetylase inhibitor panobinostat strongly enhanced the ancistrocladinium A-induced apoptosis. Mass spectrometry with biotinylated ancistrocladinium A revealed significant enrichment of RNA-splicing-associated proteins. Affected RNA-splicing-associated pathways included genes involved in proteotoxic stress response, such as PSMB5-associated genes and the heat shock proteins HSP90 and HSP70. Furthermore, we found strong induction of ATF4 and the ATM/H2AX pathway, both of which are critically involved in the integrated cellular response following proteotoxic and oxidative stress. Taken together, our data indicate that ancistrocladinium A targets cellular stress regulation in MM and improves the therapeutic response to PIs or overcomes PI resistance, and thus may represent a promising potential therapeutic agent.},
  language  = {en}
}
@phdthesis{MufusamaKoySita2019,
  author    = {Mufusama Koy Sita, Jean-Pierre},
  title     = {Quality Assessment of Antimalarial Medicines Sold in the Democratic Republic of the Congo and Phytochemical Investigations on a Congolese Ancistrocladus Liana},
  doi       = {10.25972/OPUS-19238},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192382},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Nowadays, the management of infectious diseases is especially threatened by the rapid emergence of drug resistance. It has been suggested that the medicine quality assurance combined with good medication adherence may help to reduce this impendence. Moreover, the search for new antimicrobial agents from medicinal plants is strongly encouraged for the exploration of alternatives to existing therapies. In this context, the present work focused on both the quality evaluation of commercialized antimalarial medicines from the Democratic Republic of the Congo and on the phytochemical investigations of a Congolese Ancistrocladus species.},
  subject      = {Antimalariamittel},
  language  = {en}
}
@phdthesis{Faber2007,
  author    = {Faber, Johan Henrik},
  title     = {Naphthylisoquinoline Alkaloids : Structural Elucidation, Metabolism and Functional Analysis of their Bioactivities},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22789},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {This thesis deals with the isolation and structural elucidation of bioactive naphthylisoquinoline alkaloids and related analogs. The mode of action of the antiplasmodial activity exhibited by the naphthylisoquinoline alkaloids was explored and compared to that of the antimalarial drug chloroquine. Furthermore, the phase 1 and 2 metabolism of dioncophyllines A and C and dioncopeltine A were investigated. In detail the following results have been obtained: • From the leaves of the recently discovered East African liana A. tanzaniensis six naphthylisoquinoline alkaloids were isolated. • The leaves of a botanical yet undescribed Ancistrocladus species, collected by Prof. Dr. V. Mudogo in the Democratic Republic of Congo in the habitat Yeteto near the town Ikela, were analyzed for naphthylisoquinoline alkaloids for the first time. The isolation work led to the first identification of an N,C-coupled naphthyldihydroisoquinoline alkaloid; ancistrocladinium B. Phytochemical investigation of the roots of the Congolese Ancistrocladus species (habitat Yeteto), , afforded five new derivatives of known naphthylisoquinoline alkaloids, namely 5'-O-demethylhamatine, 5'-O-demethylhamatinine, 6-O-demethylancistroealaine A, 6,5'-O,O-didemethylancistroealaine A, and 5-epi-6-O-methylancistrobertsonine A, along with six known naphthylisoquinoline alkaloids. • The antiplasmodial activity guided purification of 60Co irradiated samples containing commercially available naphthylisoquinoline related substances, afforded the isolation of the irradiation products 3,4-dihydro-1-isoquinolinone, 3,4-dihydro-1-isoquinolineamine, and 1,2,3,4-tetrahydro-1,2-diazirino-isoquinoline. The compounds were found to be more active than the starting material, although only exhibiting weak antiplasmodial activity against P. falciparum. • The effect on the absorption spectrum of FPIX due to complex formation with the naphthylisoquinoline alkaloids dioncophyllines A and C, dioncopeltine A korupensamine A, and ancistrocladine was examined by a titration study. Job's plot analyses by UV-spectroscopy determined the stoichiometry for the complex formation of FPIX and naphthylisoquinoline alkaloids to be 2:1. Furthermore, the dissociation constants for the complexation with FPIX were determined for each of the naphthylisoquinoline alkaloids investigated. Dioncophylline C and dioncopeltine A were found to possess dissociation constants, which are comparable to the one reported for the antimalarial drug chloroquine. The ability of ESI to transfer noncovalent solution-phase assemblies intact into the gas phase, was conducted on solution mixtures of naphthylisoquinoline alkaloid and FPIX, as well as on mixtures of chloroquine and FPIX. The mass spectrometry analyses revealed several peaks, which corresponded to the complex formation of FPIX to the respective ligands investigated. The most interesting results obtained were the detection of peaks corresponding to the complex formation between a chelated dimer of FPIX and dioncophylline Cand of peaks corresponding to a double protonated tetramer of FPIX - consisting of two chelated \&\#61549;-oxo dimers of FPIX - in complex formation with two molecules of chloroquine. • Two phase 1 metabolism products of dioncophylline A were identified. Coelution in combination with HPLC-MS/MS, NMR, and CD investigations assigned the major metabolic product as 5'-O-demethyldioncophylline A. The minor metabolic product was only present in small amounts, which disabled an unambiguous structural characterization of the compound. However, as deduced from the mass spectrometry analyses and exclusion of a possible metabolic oxidation product by coelution with authentic reference material, the metabolite should possess a 4-hydroxylated isoquinoline portion and is assumed to be represented by structure. Dioncophylline C and dioncopeltine A were found to be stable to phase 1 metabolism reactions caused by rat liver microsomes.},
  subject      = {Naphthylisochinolinalkaloide},
  language  = {en}
}