Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents

  • Bioorg Med Chem Lett. 2018 Feb 15;28(4):673-676. doi: 10.1016/j.bmcl.2018.01.020.
Chada Raji Reddy  1 ,  Amol Gorgile Tukaram  2 ,  Siddique Z Mohammed  3 ,  Uredi Dilipkumar  3 ,  Bathini Nagendra Babu  2 ,  Sumana Chakravarty  4 ,  Dwaipayan Bhattacharya  5 ,  Pranav C Joshi  5 ,  René Grée  6
Affiliations
  • 1. Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: [email protected].
  • 2. National Institute of Pharmaceutical Education and Research, Hyderabad 500037 India.
  • 3. Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 4. Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: [email protected].
  • 5. Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 6. Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Avenue du Général Leclerc, 35042 Rennes Cedex, France.
PMID: 29402744 DOI: 10.1016/j.bmcl.2018.01.020
Abstract

Longanlactone analogues were synthesized using a route featuring Friedel-Crafts acylation, Sonogashira coupling and 1,3-dipolar cycloaddition reactions. Structure-activity relationships were investigated for neurotrophic activity. Compound 6 was found to have the most potent neurotrophic activity among all the synthesized analogues in Neuro2a cells as evidenced by a battery of in vitro/cell based assays for assessment of neurogenic and potential neurotrophic activity including neurite outgrowth assay and real time PCR for popular markers of augmented neurotrophic activity. Compound 6 might serve as a template for further development of highly effective neurotrophic molecules.

Keywords
Longanlactone; Neurotrophic agent; Pyrrole alkaloid.
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