Synthesis, antiinflammatory activity and platelet antiaggregating activity of a new series of beta-aminoxypropionic acids.
A series of beta-aminoxypropionic acids (AOPAs) had previously been designed and synthesised as analogues of antiinflammatory arylacetic acids (ArAAs) in which the Ar portion is substituted by the (methyleneaminoxy) methyl moiety (C = NOCH2, MAOMM). Most of these AOPAs had exhibited a significant antiinflammatory and antiaggregating activity. This paper reports the synthesis of a new series of beta-aminoxypropionic acids (SAOPAs) which include the saturated (methylaminoxy)methyl moiety (CHNH-OCH2, SMAOMM) in the place of the MAOMM present in AOPAs. The antiinflammatory activity of SAOPAs was evaluated by the carrageenan-induced paw edema method and the antiaggregating activity was evaluated by means of tests using arachidonic acid (AA) and adenosine diphosphate (ADP) as the aggregating agents. Two SAOPAs were evaluated for their capacity to inhibit the cyclooxygenase enzyme by measuring the malondialdehyde (MDA) produced by incubation of sodium arachidonate with platelet-rich plasma (PRP). The pharmacological results showed that the saturation of the iminic double bond led to a reduction or even the disappearance of the antiaggreganting activity, whereas it did not induce any evident changes in the antiinflammatory activity. Theoretical studies were carried out in order to compare the conformation and the molecular reactivity of SAOPAs with those of AOPAs.
Macchia
B
B
Dipartimento di Scienze Farmaceutiche, Università di Pisa.
Macchia
M
M
Martinelli
A
A
Orlandini
E
E
Rossello
A
A
Bertini
S
S
Luchetti
E
E
Gervasi
G
G
Catalani
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan / Q000037:antagonists & inhibitors; D004487:Edema / Q000188:drug therapy; D005260:Female; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D011422:Propionates; D002351:Carrageenan