Unser 10. Leibniz Plant Biochemistry Symposium am 7. und 8. Mai war ein großer Erfolg. Thematisch ging es in diesem Jahr um neue Methoden und Forschungsansätze der Naturstoffchemie. Die exzellenten Vorträge über Wirkstoffe…
Omanische Heilpflanze im Fokus der Phytochemie IPB-Wissenschaftler und Partner aus Dhofar haben jüngst die omanische Heilpflanze Terminalia dhofarica unter die phytochemische Lupe genommen. Die Pflanze ist reich an…
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…
Nagia, M.; Morgan, I.; Gamel, M. A.; Farag, M. A.;Maximizing the value of indole-3-carbinol, from its distribution in dietary sources, health effects, metabolism, extraction, and analysis in food and biofluidsCrit. Rev. Food Sci. Nutr.648133-8154(2024)DOI: 10.1080/10408398.2023.2197065
Indole-3-carbinol (I3C) is a major dietary component produced in Brassica vegetables from glucosinolates (GLS) upon herbivores’ attack. The compound is gaining increasing interest due to its anticancer activity. However, reports about improving its level in plants or other sources are still rare. Unfortunately, I3C is unstable in acidic media and tends to polymerize rendering its extraction and detection challenging. This review presents a multifaceted overview of I3C regarding its natural occurrence, biosynthesis, isolation, and extraction procedure from dietary sources, and optimization for the best recovery yield. Further, an overview is presented on its metabolism and biotransformation inside the body to account for its health benefits and factors to ensure the best metabolic yield. Compile of the different analytical approaches for I3C analysis in dietary sources is presented for the first time, together with approaches for its detection and its metabolism in body fluids for proof of efficacy. Lastly, the chemopreventive effects of I3C and the underlying action mechanisms are summarized. Optimizing the yield and methods for the detection of I3C will assist for its incorporation as a nutraceutical or adjuvant in cancer treatment programs. Highlighting the complete biosynthetic pathway and factors involved in I3C production will aid for its future biotechnological production.
Publikation
Morgan, I.; Rennert, R.; Berger, R.; Jelača, S.; Maksimović-Ivanić, D.; Dunđerović, D.; Mijatović, S.; Kaluđerović, G. N.; Wessjohann, L. A.;The impact of 9-azaglycophymine and phenylguanidine derivatives on the proliferation of various breast cancer cell lines in vitro and in vivoSci. Rep.1428126(2024)DOI: 10.1038/s41598-024-71624-8
Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight.
Publikation
Llanes, D.; Rennert, R.; Jänicke, P.; Morgan, I.; Reguera, L.; Rivera, D. G.; Ricardo, M. G.; Wessjohann, L. A.;Development of bombesin-tubulysin conjugates using multicomponent chemistry to functionalize both the payload and the homing peptideFrontiers in Pharmacology151408091(2024)DOI: 10.3389/fphar.2024.1408091
Peptide-drug conjugates (PDCs) have recently gained significant attention for the targeted delivery of anticancer therapeutics, mainly due to their cost-effective and chemically defined production and lower antigenicity compared to ADCs, among other benefits. In this study, we designed and synthesized novel PDCs by conjugating new thiol-functionalized tubulysin analogs (tubugis) to bombesin, a peptide ligand with a relevant role in cancer research. Two tubulysin analogs bearing ready-for-conjugation thiol groups were prepared by an on-resin multicomponent peptide synthesis strategy and subsequently tested for their stand-alone in vitro anti-proliferative activity against human cancer cells, which resulted in IC50 values in the nanomolar range. In addition, various fluorescently labeled [K5]-bombesin(6–14) peptides, non-lipidated and lipidated with fatty acid chains of variable length, were also synthesized using the versatile multicomponent chemistry. These bombesin derivatives were tested for their gastrin-related peptide receptor (GRPR)-mediated internalization into cancer cells using flow cytometry, proving that the lipid tail (especially C14) enhances the cell internalization. Using the tubugi toxins and bombesin peptides, three different bombesin-tubugi conjugates were synthesized with different cleavage propensity and lipophilicity. Preliminary in vitro experiments revealed that, depending on the linker and the presence of a lipid tail, these novel PDCs possess good to potent anticancer activity and moderate selectivity for GRPR-overexpressing cancer cells.
Publikation
Lam, Y. T. H.; Schmitz, L. M.; Huymann, L.; Dhar, D.; Morgan, I.; Rennert, R.; Davari, M. D.; Peintner, U.; Palfner, G.; Arnold, N.;Cortinarius steglichii: a taxonomical and chemical novelty from ChileMycol. Prog.2355(2024)DOI: 10.1007/s11557-024-01983-z
The new species Cortinarius steglichii is described from Chilean Nothofagus forest based on morphological and microscopical attributes, molecular phylogeny, and chemical analysis of secondary metabolites. C. steglichii is characterized by abundant, long, ramified cystidia on the lamellar edges and stipe apex, further by a deep violet color reaction after treatment with KOH. As responsible secondary metabolite for the cytoplasmatic color reaction of cystidia and some hyphae, the new diterpenoid steglichon (1) could be recognized, showing also remarkable antibacterial and anticancer activity. Phylogenetic analyses (ITS, LSU, RPB1) confirm the close relationship to species of the Cortinarius dulciolens group.