PM100117 and PM100118, new antitumor macrolides produced by a marine Streptomyces caniferus GUA-06-05-006A

• Published in: Journal of antibiotics 2016-05, Vol.69 (5), p.388-394
• Main Authors: Pérez, Marta, Schleissner, Carmen, Fernández, Rogelio, Rodríguez, Pilar, Reyes, Fernando, Zuñiga, Paz, de la Calle, Fernando, Cuevas, Carmen
• Format: Article
• Language: English
• Subjects: 101/47; 101/58; 38/22; 38/77; 631/154/349; 706/648/479/429; A549 Cells; Antifungal Agents - pharmacology; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Breast Neoplasms - drug therapy; Candida albicans - drug effects; Cell Line, Tumor; Cell Membrane - drug effects; Cell Membrane Permeability - drug effects; Cell Proliferation - drug effects; Colonic Neoplasms - drug therapy; Cytotoxicity; Female; Humans; Life Sciences; Lung Neoplasms - drug therapy; Macrolides - isolation & purification; Macrolides - pharmacology; Medicinal Chemistry; Microbiology; Organic Chemistry; original-article; Streptomyces - metabolism
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2015.121

Two new bioactive polyhydroxyl macrolide lactones PM100117 ( 1 ) and PM100118 ( 2 ) were isolated from the culture broth of the marine-derived Streptomyces caniferus GUA-06-05-006A. Their structures were elucidated by a combination of spectroscopic methods, mainly one-dimensional and 2D NMR and HRESI-MS. They consist of 36-membered macrolides with a side chain containing three deoxy sugars and a 1,4-naphthoquinone chromophore. Compounds 1 and 2 displayed potent cytotoxicity against three human tumor cell lines with GI 50 values in the micromolar range, as well as slight antifungal activity against Candida albicans ATCC10231. In addition, both compounds alter the plasma membrane of tumor cells, inducing loss of membrane integrity and subsequent cell permeabilization leading to a fast and dramatic necrotic cell death.