Synthesis and biological evaluation of substituted quinazoline derivatives
Keywords:
1,3,4-oxadiazole, quinazoline, anti convulsant activity, CHN analysis, NMRAbstract
A new series of Quinazoline-oxadiazole analogues was designed, synthesized, and evaluated for anticonvulsant action against chemically induced seizures and compared with the reference drugs valproate., compounds Q4, Q8, Q10, and Q11 provided 70-100% protection against PTZ-induced seizure. FTIR, 1H- nuclear magnetic resonance, and mass spectrometry (MS) spectra analyses were used to determine the structure of the produced molecules. For all newly synthesised drugs, molecular docking was used to test their binding affinities towards the GABA-A receptor in effort to qualitatively justify their anticonvulsant actions. The results of molecular modelling were correlated with the results of biological screening. As GABAA receptor agonists,Compounds Q4, Q8, Q10, and Q11 have the highest binding affinities to the GABA-A receptor as well as the strongest anticonvulsant activity in mice. The results demonstrated that the majority of active compounds might be used as a template for future creation, adaption, and exploration to create more active analogues
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