Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents

Evaluation of neurotrophic activity of longanlactone along with its analogues has been achieved for the first time. A total of 12-analogues have been prepared including C4-epimers. [Display omitted] •Longanlactone, a natural pyrrole-lactone alkaloid, analogs were synthesized.•Neurotrophic effects of...

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Published in:Bioorganic & medicinal chemistry letters 2018-02, Vol.28 (4), p.673-676
Main Authors: Reddy, Chada Raji, Tukaram, Amol Gorgile, Mohammed, Siddique Z., Dilipkumar, Uredi, Babu, Bathini Nagendra, Chakravarty, Sumana, Bhattacharya, Dwaipayan, Joshi, Pranav C., Grée, René
Format: Article
Language:English
Subjects:
Animals
Brain-Derived Neurotrophic Factor - genetics
Cell Line, Tumor
Chemical Sciences
Drug Design
Lactones - chemical synthesis
Lactones - pharmacology
Lactones - toxicity
Longanlactone
Medicinal Chemistry
Mice
Molecular Structure
Neuronal Outgrowth - drug effects
Neurotrophic agent
Organic chemistry
Pyrrole alkaloid
Pyrroles - chemical synthesis
Pyrroles - pharmacology
Pyrroles - toxicity
RNA, Messenger - metabolism
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Summary:Evaluation of neurotrophic activity of longanlactone along with its analogues has been achieved for the first time. A total of 12-analogues have been prepared including C4-epimers. [Display omitted] •Longanlactone, a natural pyrrole-lactone alkaloid, analogs were synthesized.•Neurotrophic effects of Longanlactone analogs were studied for the first time.•mRNA Fold change was observed in BDNF gene expression study of Longanlactone. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2018.01.020