Mohareb R.M.Ahmed H.H.Elmegeed G.A.Abd-Elhalim M.M.Shafic R.W.Organic Chemistry DepartmentFaculty of PharmacyOctober University of Modern Sciences and Arts (MSA)October CityEgypt; Chemistry DepartmentFaculty of ScienceCairo UniversityCarioEgypt; Hormones DepartmentNational Research CentreDokki 12622CairoEgypt2020-01-252020-01-2520119680896https://doi.org/10.1016/j.bmc.2011.03.031PubMed ID 21493072https://t.ly/GJPrkScopusThere is a great deal of interest in neurotrophin therapy to prevent neuronal degeneration. The present study aimed at synthesizing new functionalized indole derivatives with structures justifying neuroprotective activity using l-tryptophan (TRP)� as starting material. The potential neuroprotective effect of these newly synthesized agents against acrylamide (ACR) induced neurotoxicity was investigated in adult female rats. The novel indole derivatives, indolylmethyl pyridine derivatives 9a,b, pyrimidinylindolyl propanone derivatives 12a-c, pyrazolylindolyl propanone derivatives 14a,b, and indolyl tetrazolopropanoic acid derivative 17 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [ip, 50 mg kg -1 body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with the indole derivatives 9b, 12c, 14a, and 17 (ip, 50 mg kg-1 b. wt.) prior to ACR produced neuroprotective activity with various intensities depending on the structure of each compound. Compound 17 in which the tetrazole ring was attached to the TRP moiety ranked as the strongest neuroprotective agent. All the tested compounds have been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by ACR administration. � 2011 Elsevier Ltd. All rights reserved.EnglishIndoleNeuroprotectivePyrazolePyridinePyrimidineTetrazoleTryptophan1 (3,5 diamino 4,5 dihydro 1 phenylpyrazol 4 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 one1 (3,5 diamino 4,5 dihydro 1h pyrazol 4 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 one1 (4,6 diamino 2 imino 5h pyrimidin 5 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 one1 (4,6 diamino 2 oxo 5h pyrimidin 5 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 one1 (4,6 diamino 2 thioxo 5h pyrimidin 5 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 one2 (1h tetrazole 5 methylencarboxamido) 3 (1h indol 3 yl)propanoic acid2 [(1h indol 3 yl)methyl] 5 amino 3 (phenylamino)pyridine 4 carbonitrile2 cyano 5 (1h indol 3 yl) 4 (methylenamino) 3 oxopentanonitrile3 (1h indol 3 yl) 2 (methylenamino) n phenylpropanamide3 (1h indol 3 yl) 2 (methylenamino)propanoic acid3 (1h indol 3 yl) 2 (methylenamino)propanoyl chlorideacrylamideethyl 2 [(1h indol 3 yl)methyl] 5 amino 3 (phenylamino)pyridine 4 carboxylateindole derivativeindolylmethylpyridine derivativelactate dehydrogenasemalonaldehydepyrazolylindoylmethylenaminopropan 1 one derivativepyrimidinylindolylmethylenamino propan 1 one derivativeunclassified druganimal experimentanimal modelanimal tissueantioxidant activityarticlecarbon nuclear magnetic resonancecontrolled studycrystallizationdrug efficacydrug structuredrug synthesisenzyme activityfemaleglutathione metabolismlipid peroxidationneuroprotectionneurotoxicityneurotransmissionnonhumanoxidative stressproton nuclear magnetic resonanceratroom temperatureAnimalsBrainFemaleGlutathioneGlutathione PeroxidaseIndolesLactate DehydrogenasesMalondialdehydeNeuroprotective AgentsPropionic AcidsRatsRats, Sprague-DawleySuperoxide DismutaseRattusArticlehttps://doi.org/10.1016/j.bmc.2011.03.031PubMed ID 21493072