Osmanicin, a Polyketide Alkaloid Isolated from <i>Streptomyces osmaniensis</i> CA-244599 Inhibits Elastase in Human Fibroblasts
Mamdouh N. Samy,
Géraldine Le Goff,
Philippe Lopes,
Katerina Georgousaki,
Sentiljana Gumeni,
Celso Almeida,
Ignacio González,
Olga Genilloud,
Ioannis Trougakos,
Nikolas Fokialakis,
Jamal Ouazzani
Affiliations
Mamdouh N. Samy
Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
Géraldine Le Goff
Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
Philippe Lopes
Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
Katerina Georgousaki
Department of Pharmacognosy & Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece
Sentiljana Gumeni
Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece
Celso Almeida
Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, 18016 Granada, Spain
Ignacio González
Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, 18016 Granada, Spain
Olga Genilloud
Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, 18016 Granada, Spain
Ioannis Trougakos
Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece
Nikolas Fokialakis
Department of Pharmacognosy & Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece
Jamal Ouazzani
Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
The strain Streptomyces osmaniensis CA-244599 isolated from the Comoros islands was submitted to liquid-state fermentation coupled to in situ solid-phase extraction with amberlite XAD-16 resin. Elution of the trapped compounds on the resin beads by ethyl acetate afforded seven metabolites, osmanicin (1), streptazolin (2), streptazone C (3), streptazone B1 (4), streptenol C (5), nocardamine (6) and desmethylenylnocardamine (7). Osmanicin (1) is a newly reported unusual scaffold combining streptazolin (2) and streptazone C (3) through a Diels-Alder type reaction. Experimental evidence excluded the spontaneous formation of 1 from 2 and 3. The isolated compounds were evaluated for their ability to inhibit elastase using normal human diploid fibroblasts. Compound 1 exhibited the most potent activity with an IC50 of 3.7 μM.
