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Synthesis and Antidepressant Evaluation of Five Novel Heterocyclic Tryptophan‐Hybrid Derivatives
Author(s) -
Elmegeed Gamal A.,
Baiuomy Ayman R.,
Abdelhalim Mervat M.,
Hana Hanaa Y.
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900244
Subject(s) - chemistry , antidepressant , tryptophan , behavioural despair test , chemical synthesis , reactivity (psychology) , sedative , acute toxicity , stereochemistry , in vitro , organic chemistry , pharmacology , toxicity , amino acid , biochemistry , medicine , alternative medicine , pathology , neuroscience , hippocampus , biology
This study aimed at evaluating the reactivity of L ‐Tryptophan (TRP) 1 towards various chemical reagents to produce new bi‐ and tri‐heterocyclic systems providing basic pharmacological activities. Indol‐3‐yl hydroxyoxazol‐2‐yl acetonitrile derivatives 5 and 6 , indol‐3‐yl‐hydroxyoxazol‐2‐yl‐1,2,4‐triazine derivatives 8 and 9, indol‐3‐yl‐hydroxyoxazol‐2‐yl‐aminopyrazole derivatives 11a, b, and indol‐3‐yl‐hydroxyoxazol‐2‐yl‐aminoisoxazole derivative 12 were synthesized via straightforward and efficient methods. The structures were characterized by spectral data (IR, 1 H‐NMR, 13 C‐NMR, and MS) and the purity was ascertained by microanalysis. Also, this work was extended to study the potential role of the novel synthesized TRP derivatives 5 , 6 , 9 , 11a , and 12 as antidepressant and sedative agents in comparison with TRP. All compounds showed significant antidepressant activity in the forced‐swimming test at two doses (50 or 100 mg/kg). Also, all tested compounds (at 50 or 100 mg/kg) produced a significant decrease in locomotor activity of mice during a 30 min observation period. The most potent antidepressant and sedative effect was produced by the tri‐heterocyclic compounds 9 and 12 , followed by 11a and TRP.