title: Caspase-3 activation in human melanoma A375 cell line by a novel selective sigma-2 agonist.
abstract: Two novel 8-azabicyclo[3.2.1]octan-3-ol derivatives, 11a and 11b, with high affinity for sigma-2 receptors and a very good sigma-1/sigma-2 selectivity ratio were synthesized. In comparison with several well established sigma-2 selective ligands, 11 b showed a very low sigma-1 receptor affinity. Functional assays demonstrated that 11b acts as an agonist and in A-375 human melanoma cell line is able to lower levels of procaspase-3, thus confirming a potential major role for sigma-2 pure agonists in the treatment of rapid proliferating melanoma cells.
authors.forename: S
authors.initials: S
authors.lastname: Ronsisvalle
authors.forename: G
authors.initials: G
authors.lastname: Arico
authors.forename: A M
authors.initials: AM
authors.lastname: Cova
authors.forename: P
authors.initials: P
authors.lastname: Blanco
authors.forename: E
authors.initials: E
authors.lastname: Amata
authors.forename: M
authors.initials: M
authors.lastname: Pappalardo
authors.forename: L
authors.initials: L
authors.lastname: Pasquinucci
authors.forename: A
authors.initials: A
authors.lastname: Spadaro
authors.forename: N
authors.initials: N
authors.lastname: Ronsisvalle
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000201:enzymology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects*; D013379:Substrate Specificity; D000097605:Sigma-1 Receptor
chemical_list: D053148:Caspase 3; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor; C505407:CASP3 protein, human