Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Mpetga, J. D. S.; Nago, R. D. T.; Tamokou, J.-D.-D.; Fobofou, S. A. T.; Bitchagno, G. T. M.; Wessjohann, L. A.; Tene, M.; Ngouela, A. S.;A new ceramide from Cissus aralioides Baker (Vitaceae) and its antimicrobial activityChem. Biodivers.19e202200678(2022)DOI: 10.1002/cbdv.202200678
Purification through repeated column chromatography over silica gel and Sephadex LH-20 of the ethanol extract of the stems of Cissus aralioides (Baker) Planch. resulted in the isolation of a new ceramide, aralioidamide A (1) along with five known compounds (2-6). Their structures were determined by the extensive analysis of their spectroscopic (1D and 2D NMR) and spectrometric data, and comparison with those reported in the literature. Aralioidamide A (1) displayed weak antibacterial activity (MIC = 256 μg/mL) against Bacillus subtilis, Staphylococcus aureus and Shigella flexneri and was inactive (MIC > 256 μg/mL) against the tested fungi.
Publikation
Méndez, Y.; De Armas, G.; Pérez, I.; Rojas, T.; Valdés-Tresanco, M. E.; Izquierdo, M.; Alonso del Rivero, M.; Álvarez-Ginarte, Y. M.; Valiente, P. A.; Soto, C.; de León, L.; Vasco, A. V.; Scott, W. L.; Westermann, B.; González-Bacerio, J.; Rivera, D. G.;Discovery of potent and selective inhibitors of the Escherichia coli M1-aminopeptidase via multicomponent solid-phase synthesis of tetrazole-peptidomimeticsEur. J. Med. Chem.163481-499(2019)DOI: 10.1016/j.ejmech.2018.11.074
The Escherichia coli neutral M1-aminopeptidase (ePepN) is a novel target identified for the development of antimicrobials. Here we describe a solid-phase multicomponent approach which enabled the discovery of potent ePepN inhibitors. The on-resin protocol, developed in the frame of the Distributed Drug Discovery (D3) program, comprises the implementation of parallel Ugi-azide four-component reactions with resin-bound amino acids, thus leading to the rapid preparation of a focused library of tetrazole-peptidomimetics (TPMs) suitable for biological screening. By dose-response studies, three compounds were identified as potent and selective ePepN inhibitors, as little inhibitory effect was exhibited for the porcine ortholog aminopeptidase. The study allowed for the identification of the key structural features required for a high ePepN inhibitory activity. The most potent and selective inhibitor (TPM 11) showed a non-competitive inhibition profile of ePepN. We predicted that both diastereomers of compound TPM 11 bind to a site distinct from that occupied by the substrate. Theoretical models suggested that TPM 11 has an alternative inhibition mechanism that doesn't involve Zn coordination. On the other hand, the activity landscape analysis provided a rationale for our findings. Of note, compound TMP 2 showed in vitro antibacterial activity against Escherichia coli. Furthermore, none of the three identified inhibitors is a potent haemolytic agent, and only two compounds showed moderate cytotoxic activity toward the murine myeloma P3X63Ag cells. These results point to promising compounds for the future development of rationally designed TPMs as antibacterial agents.
Publikation
Shaaban, S.; Ashmawy, A. M.; Negm, A.; Wessjohann, L. A.;Synthesis and biochemical studies of novel organic selenides with increased selectivity for hepatocellular carcinoma and breast adenocarcinomaEur. J. Med. Chem.179515-526(2019)DOI: 10.1016/j.ejmech.2019.06.075
Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.
Publikation
Bürstenbinder, K.; Mitra, D.; Quegwer, J.;Functions of IQD proteins as hubs in cellular calcium and auxin signaling: A toolbox for shape formation and tissue-specification in plants?Plant Signal Behav.12e1331198(2017)DOI: 10.1080/15592324.2017.1331198
Calcium (Ca2+) ions play pivotal roles as second messengers in intracellular signal transduction, and coordinate many biological processes. Changes in intracellular Ca2+ levels are perceived by Ca2+ sensors such as calmodulin (CaM) and CaM-like (CML) proteins, which transduce Ca2+ signals into cellular responses by regulation of diverse target proteins. Insights into molecular functions of CaM targets are thus essential to understand the molecular and cellular basis of Ca2+ signaling. During the last decade, IQ67-domain (IQD) proteins emerged as the largest class of CaM targets in plants with mostly unknown functions. In the March issue of Plant Physiology, we presented the first comprehensive characterization of the 33-membered IQD family in Arabidopsis thaliana. We showed, by analysis of the subcellular localization of translational green fluorescent protein (GFP) fusion proteins, that most IQD members label microtubules (MTs), and additionally often localize to the cell nucleus or to membranes, where they recruit CaM Ca2+ sensors. Important functions at MTs are supported by altered MT organization and plant growth in IQD gain-of-function lines. Because IQD proteins share structural hallmarks of scaffold proteins, we propose roles of IQDs in the assembly of macromolecular complexes to orchestrate Ca2+ CaM signaling from membranes to the nucleus. Interestingly, expression of several IQDs is regulated by auxin, which suggests functions of IQDs as hubs in cellular auxin and calcium signaling to regulate plant growth and development.