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Synthesis and Evaluation of Novel Marine Bromopyrrole Alkaloid‐Based Derivatives as Potential Antidepressant Agents
Author(s) -
Rane Rajesh A.,
Napahde Shital,
Bangalore Pavan Kumar,
Sahu Niteshkumar U.,
Shah Nishant,
Kulkarni Yogesh A.,
Barve Kalyani,
Lokare Leena,
Karpoormath Rajshekhar
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12352
Subject(s) - antidepressant , chemistry , behavioural despair test , fluoxetine , pharmacology , tail suspension test , stereochemistry , imipramine , alkaloid , potency , in vitro , biochemistry , medicine , serotonin , receptor , alternative medicine , pathology , hippocampus
Herein, we report synthesis and screening of a series of twenty derivatives of bromopyrrole alkaloids with aroyl hydrazone feature for antidepressant activity by forced swim test ( FST ), tail suspension test ( TST ), and actophotometer method. The molecules were further evaluated for in vitro human MAO 's inhibitory activities. The tested compounds exhibited moderate to good antidepressant activity compared with standard fluoxetine. Among these, most promising antidepressant derivatives 5b (% DID = 60.48), 5e (% DID = 59), and 5j (% DID = 74.86) reduced immobility duration of 50–70% at 30 mg/kg dose levels in FST . Further, derivative 5b , 5e, and 5j displayed good antidepressant activity with % DID value of 47.50, 46.62, and 52.49, respectively, in TST compared with standard fluoxetine (66.56% DID ). Compound 5b showed high in vitro MAO ‐A potency and selectivity ( K i MAO ‐A ( μ m ) = 2.4 ± 0.99, SI = 0.06) with promising pharmacological activity recognizing its potential as antidepressant lead candidate for further drug development. Study revealed that the presence of halogen atoms such as chlorine and fluorine at ortho ‐ and/or para ‐position of phenyl ring and N ‐alkylation of pyrrole core is favored features for antidepressant activity.