Synthesis and biological activities of some new (Nα-dinicotinoyl)-bis-L-leucyl linear and macrocyclic peptides

Molecules. 2014 Jul 24;19(8):10698-716. doi: 10.3390/molecules190810698.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / chemical synthesis
  • Anti-Infective Agents / pharmacology
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Bacteria / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemistry Techniques, Synthetic
  • Edema / chemically induced
  • Edema / drug therapy
  • Fungi / drug effects
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Peptides, Cyclic / administration & dosage
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / pharmacology*
  • Pyridines / chemistry
  • Rats
  • Xenograft Model Antitumor Assays

Substances

  • 3,5-pyridinedicarboxylic acid
  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Peptides, Cyclic
  • Pyridines