Abstract
In continuation to our search for new amino acid and peptide based anti-inflammatory agents, the suggestion, synthesis, structure elucidation of some N
-bis-dipicolinoyl amino acids, linear tetra and cyclic octa bridged peptides 1-9, of which four are new compounds 6-9, were herein realized. Accordingly, N
-bis-dipicolinoyl-L-leucine methyl ester 1, the corresponding acid 2, its bis-DL-norvalyl methyl ester homologue 3, the acid 4 and hydrazide 5 analogues were conventionally prepared.
The tetrachlorophthalic acid hydrazine conjugate 6, anisaldehyde hydrazone 7, the benzenetetracarboxylic acid and naphthalenetetracarboxylic acid bis-L-leucyl-DL-norvalyl cyclic octa bridged peptides 8 and 9 respectively, were newly synthesized via condensation of the hydrazide 5 with the corresponding aldehyde or anhydride.
The chromatographic, IR, NMR and mass spectral analysis confirmed the identities of the synthesized compounds.
Comparable to the two reference antiinflammatory drugs indomethacin
and voltaren
(100%), the determined antiinflammatory potency of the candidates (carrageenan
induced paw edema in rats) revealed a general significant activity (66 - 94%), except for the practically inactive 6 (∼1.5 % activity).
In particular, the potency of the (N
-dipicolinoyl)-bis-L-leucyl-DL-norvalyl anisaldehyde hydrazone 7 was of 94 and 87%, comparable to the reference drugs. However, 7 also showed 58% protection against ulcer formation, comparable to null for indomethacin
. Additionally, an acceptable acute toxicity was observed (LD
: 2833 mg/kg, comparable to 2700 and 2850 for indomethacin
and voltaren
respectively).