title: New, non-quinone fluorogeldanamycin derivatives strongly inhibit Hsp90.
abstract: Streptomyces hygroscopicus is a natural producer of geldanamycin. Mutasynthetic supplementation of an AHBA-blocked mutant with all possible monofluoro 3-aminobenzoic acids provided new fluorogeldanamycins. These showed strong antiproliferative activity and inhibitory effects on human heat shock protein Hsp90. Binding to Hsp90 in the low nanomolar range was determined from molecular modelling, AFM analysis and by calorimetric studies.
authors.affiliation: Institute of Organic Chemistry, Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover (Germany).
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Hermane
authors.forename: Ilona
authors.initials: I
authors.lastname: Bułyszko
authors.forename: Simone
authors.initials: S
authors.lastname: Eichner
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.forename: Wera
authors.initials: W
authors.lastname: Collisi
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
authors.forename: Emilia
authors.initials: E
authors.lastname: Schax
authors.forename: Johanna-Gabriela
authors.initials: JG
authors.lastname: Walter
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheper
authors.forename: Klaus
authors.initials: K
authors.lastname: Kock
authors.forename: Christian
authors.initials: C
authors.lastname: Herrmann
authors.forename: Pooyan
authors.initials: P
authors.lastname: Aliuos
authors.forename: Günter
authors.initials: G
authors.lastname: Reuter
authors.forename: Carsten
authors.initials: C
authors.lastname: Zeilinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Kirschning
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005464:Fluorobenzenes / Q000378:metabolism / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D011809:Quinones / Q000737:chemistry; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D062368:meta-Aminobenzoates / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D005464:Fluorobenzenes; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D062368:meta-Aminobenzoates; C001277:geldanamycin
keywords: Hsp90; fluorinated compounds; geldanamycin; inhibitors; mutasynthesis; single molecule force spectroscopy