Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities

Bioorg Med Chem. 2017 Feb 15;25(4):1374-1388. doi: 10.1016/j.bmc.2016.12.045. Epub 2016 Dec 29.

Abstract

A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (1H, 13C NMR and mass). Compounds 18b, 27a and 8 showed potent 5-lipoxygenase enzyme inhibitory activity (IC50: 19.53, 20.31 and 44.14μg/mL). The computational studies revealed that selectivity of AKBA is due to its fitment into the 5-LOX receptor, which is missing for the other enzymes like 12-LOX, COX-1 and COX-2. Our study found potentiating effects of 2-formyl and 3-keto substituents in reviving inactive AKBA analogues possessing essential COOH group at 4th position.

Keywords: 3-O-acetyl-11-keto-β-boswellic acid; 5-Lipoxygenase; Anti-inflammatory; Boswellia serrata.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Lipoxygenase Inhibitors / chemical synthesis
  • Lipoxygenase Inhibitors / chemistry
  • Lipoxygenase Inhibitors / pharmacology*
  • Molecular Structure
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipoxygenase Inhibitors
  • Triterpenes
  • acetyl-11-ketoboswellic acid
  • Arachidonate 5-Lipoxygenase
  • ALOX5 protein, human