title: PM100117 and PM100118, new antitumor macrolides produced by a marine Streptomyces caniferus GUA-06-05-006A.
abstract: 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 GI50 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.
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pérez
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Schleissner
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Fernández
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Rodríguez
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Reyes
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: Zuñiga
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Calle
authors.affiliation: Drug Discovery Area, PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuevas
mesh_terms: D000072283:A549 Cells; D000935:Antifungal Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D018942:Macrolides / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D018942:Macrolides; C000614291:PM100117; C000614292:PM100118