Butanolides and Butenolides from a Marine-Derived <i>Streptomyces</i> sp. Exert Neuroprotective Activity through Activation of the TrkB Neurotrophin Receptor
Paolo Giaccio,
Despoina Charou,
Dafni-Ioanna Diakaki,
Anna Chita,
Achille Gravanis,
Ioannis Charalampopoulos,
Vassilios Roussis,
Efstathia Ioannou
Affiliations
Paolo Giaccio
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Despoina Charou
Department of Pharmacology, Medical School, University of Crete, 71003 Heraklion, Greece
Dafni-Ioanna Diakaki
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Anna Chita
Department of Pharmacology, Medical School, University of Crete, 71003 Heraklion, Greece
Achille Gravanis
Department of Pharmacology, Medical School, University of Crete, 71003 Heraklion, Greece
Ioannis Charalampopoulos
Department of Pharmacology, Medical School, University of Crete, 71003 Heraklion, Greece
Vassilios Roussis
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Efstathia Ioannou
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Neurodegenerative diseases are incurable and debilitating conditions, characterized by progressive loss and degeneration of vulnerable neuronal populations. Currently, there are no effective therapies available for the treatment of most neurodegenerative disorders. A panel of extracts exhibiting interesting chemical profiles among a high number of bacterial strains isolated from East Mediterranean marine sediments and macroorganisms were evaluated for their activity on TrkB-expressing cells. Among them, the actinobacterial strain Streptomyces sp. BI0788, exhibiting neuroprotective activity in vitro, was selected and cultivated in large-scale. The chemical analysis of its organic extract resulted in the isolation of four new butanolides (1, 4–6), along with two previously reported butanolides (2 and 3) and eight previously reported butenolides (7–14). Compounds 2–4 and 7–14 were evaluated for their neuroprotective effects on TrkB-expressing NIH-3T3 cells. Among them, metabolites 3, 4, 7, 10, 11, 13 and 14 exhibited significant protective activity on the aforementioned cells through the activation of TrkB, the high-affinity receptor for the Brain-Derived Neurotrophic Factor (BDNF), which is well known to play a crucial role in neuronal cell survival and maintenance.
