Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents

Chada Raji Reddy; Amol Gorgile Tukaram; Siddique Z Mohammed; Uredi Dilipkumar; Bathini Nagendra Babu; Sumana Chakravarty; Dwaipayan Bhattacharya; Pranav C Joshi; René Grée

doi:10.1016/j.bmcl.2018.01.020

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. Epub 2018 Jan 12.

Authors

Chada Raji Reddy¹, Amol Gorgile Tukaram², Siddique Z Mohammed³, Uredi Dilipkumar³, Bathini Nagendra Babu², Sumana Chakravarty⁴, Dwaipayan Bhattacharya⁵, Pranav C Joshi⁵, René Grée⁶

Affiliations

¹ Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: rajireddy@iict.res.in.
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: sumanachak@iict.res.in.
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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain-Derived Neurotrophic Factor / genetics
Cell Line, Tumor
Drug Design
Lactones / chemical synthesis
Lactones / pharmacology*
Lactones / toxicity
Mice
Molecular Structure
Neuronal Outgrowth / drug effects*
Pyrroles / chemical synthesis
Pyrroles / pharmacology*
Pyrroles / toxicity
RNA, Messenger / metabolism

Substances

Brain-Derived Neurotrophic Factor
Lactones
Pyrroles
RNA, Messenger