Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents

Chada Raji Reddy (1) , Amol Gorgile Tukaram (2) , Siddique Z. Mohammed (1) , Uredi Dilipkumar (1) , Bathini Nagendra Babu , Sumana Chakravarty (1) , Dwaipayan Bhattacharya (1) , Pranav C. Joshi (1) , René Grée (3)

1 IICT - CSIR Indian Institute of Chemical Technology
2 NIPER - National Institute of Pharmaceutical Education and Research
3 ISCR - Institut des Sciences Chimiques de Rennes

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: Pyrrole alkaloid; Longanlactone; Neurotrophic agent

Domains: Chemical Sciences; Medicinal Chemistry; Chemical Sciences; Organic chemistry

Chada Raji Reddy, Amol Gorgile Tukaram, Siddique Z. Mohammed, Uredi Dilipkumar, Bathini Nagendra Babu, et al.. Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents. Bioorganic and Medicinal Chemistry Letters, 2018, 28 (4), pp.673-676. ⟨10.1016/j.bmcl.2018.01.020⟩. ⟨hal-01737386⟩