Synthesis and Biological Activities of Some New (Nα-Dinicotinoyl)-bis-l-Leucyl Linear and Macrocyclic Peptides

摘要

A series of linear and macrocyclic peptides >3–>12 were synthesized using 3,5-pyridinedicarboxylic acid (>1) as starting material and screened for their antimicrobial, anti-inflammatory and anticancer activities. Bis-ester >3 was prepared from >1 and l-leucine methyl ester. Hydrazinolysis and hydrolysis of dipeptide methyl ester >3 with hydrazine hydrate or 1 N sodium hydroxide afforded compounds >4 and >5, respectively. Cyclization of the dipeptide >5 with l-lysine methyl ester afforded cyclic pentapeptide ester >6. Compounds >7–>9 were synthesized by reacting hydrazide >4 with phthalic anhydride, 1,8-naphthalene anhydride or acetophenone derivatives. Treatment of acid hydrazide >4 with aromatic aldehydes or tetraacid dianhydrides afforded the corresponding bis-dipeptide hydrazones >10a–>e and macrocyclic peptides >11 and >12, respectively. The structures of newly synthesized compounds were confirmed by IR, ¹H-NMR, MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, biological and pharmacological activities of the synthesized compounds was reported.