Synthesis of 3,3'-(1-piperidino)substituted methylene-bis-isoxazoles preventing stimulus-induced leukocytes activation.
Some 3,3'-(1-piperidino)substituted methylene-bis-isoxazoles were prepared via Mannich base and tested to verify their antiinflammatory-related activity. Human neutrophils stimulated with either PMA and f-MLP were used as the cellular model. The efficiency of eight differently substituted compounds (2-9) was established on their capacity to reduce the O(2)(-) production by activated human neutrophils. The rising hydrophobicity in the side-chain of methylene-bis-isoxazoles leads to a distinction in the neutrophil response against the two stimuli, favoring the inhibition of the PMA elicited cell activation and leaving inaffected the f-MLP induced cell responses. Compounds 8 and 9 are particularly active and abolish almost completely the neutrophil activation in the presence of PMA stimulus.
Mazzei
M
M
Dipartimento di Scienze Farmaceutiche, Viale Benedetto XV, 3, Genoa 16132, Italy. mazzei@cba.unige.it
Nieddu
E
E
Melloni
E
E
Minafra
R
R
D006801:Humans; D006838:Hydrocarbons; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008697:Methane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology
D006838:Hydrocarbons; D007555:Isoxazoles; D010880:Piperidines; C030011:carbene; D008697:Methane