title: Structural modifications of bryostatin 2.
abstract: Continuation of a structure/activity relationship study of the bryostatins was focused on bryostatin 2. Stepwise catalytic hydrogenation of bryostatin 2 gave the following results. Reduction of the side-chain diene system to saturated ester 2a (P388 cell line ED50 8.5 x 10(-3) micrograms/ml) did not significantly affect the murine P388 cell line inhibition by bryostatin 2. Further hydrogenation to hexahydro derivative 2b gave a reduced P388 ED50 of 5.1 x 10(-2) micrograms/ml. Conversion to the octahydrobryostatin 2c caused a further reduction of P388 cell line activity to ED50 2.9 x 10(-1) micrograms/ml. Other structural modifications of bryostatin 2 in respect to esterification at the C-7 position significantly affected the P388 lymphocytic leukemia cell line response. Each of the bryostatin 2 derivatives was also evaluated with respect to protein kinase C binding.
authors.affiliation: Cancer Research Institute, Arizona State University, Tempe 85287-1604.
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
authors.forename: D
authors.initials: D
authors.lastname: Sengupta
authors.forename: P M
authors.initials: PM
authors.lastname: Blumberg
authors.forename: N E
authors.initials: NE
authors.lastname: Lewin
authors.forename: J M
authors.initials: JM
authors.lastname: Schmidt
authors.forename: A S
authors.initials: AS
authors.lastname: Kraft
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D054713:Bryostatins; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D007941:Leukemia P388 / Q000473:pathology; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D011493:Protein Kinase C / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C054557:bryostatin 2; D011493:Protein Kinase C