New triazole-based hybrids as neurotropic agents

Area of Science:

• Medicinal Chemistry
• Neuropharmacology
• Organic Synthesis

Background:

• Triazole derivatives are known for diverse biological activities.
• Developing novel anticonvulsant, anxiolytic, and antidepressant agents is a significant therapeutic challenge.

Purpose of the Study:

• To synthesize and evaluate novel hybrids incorporating 1,2,3- and 1,2,4-triazole moieties.
• To assess the anticonvulsant, anxiolytic, and antidepressant activities of the synthesized compounds.

Main Methods:

• Synthesis of 1,2,3-triazole hybrids via click reaction.
• Synthesis of 1,2,4-triazole hybrids from specific acetohydrazides.
• Pharmacological evaluation using pentylenetetrazole (PTZ), thiosemicarbazide (TSC), and maximal electroshock seizure (MES) models.
• Behavioral assays including open field, elevated plus maze (EPM), and forced swim test.
• Molecular docking studies.

Main Results:

• All synthesized hybrids exhibited antagonism against PTZ-induced convulsions (40-80%).
• Active compounds significantly increased latency in TSC-induced seizures (1.9-4.65 times).
• Some compounds displayed notable anxiolytic and antidepressant effects.
• Docking studies correlated well with experimental pharmacological data.
• The most potent compounds featured a pyrano[3,4-c]pyridine ring.

Conclusions:

• The synthesized triazole hybrids possess significant anticonvulsant properties.
• Certain hybrids demonstrate potential as anxiolytic and antidepressant agents.
• The pyrano[3,4-c]pyridine scaffold appears crucial for the observed activity.