Hypnotic Profile of Imines from Benzimidazole Chalcones: Mechanism of Synthesis, DFT Studies and in silico Screening
Bijo Mathew, Jerad Suresh, Sockalingam Anbazhagan and Vinod Devaraji
Affiliation: Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad 678004, Kerala, India.
A series of 1-(1H-benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene] amino}-1,3,4-thiadiazole-2-
thiols (6a-6f) were synthesized by the acid catalyzed nucleophilic addition reaction between 1-(1H-benzimidazol-2-yl)-3-
phenylprop-2-en-1-ones (4a-4f) and 5-amino-1,3,4-thiadiazole-2-thiol. All the synthesized compounds were characterised
by IR, 1HNMR, 13CNMR, Mass and elemental analyses. A transition state calculation obtained from DFT study to explore
the molecular mechanism of action of the synthetic route. The mechanism of synthesis revealed that the imidazole system
can make an increase in the electrophilic character of carbonyl carbon in the benzimidazole chalcones. So the electron
deficient carbonyl carbon could be efficiently attacked on the amino group of 1,3,4-thiadiazole ring to forms an imine
linkage between the two heterocyclic systems. All the titled derivatives at a dose level of 10mg/kg body weight potentiate
the hypnotic action of Phenobarbitone (at a dose of 10mg/kg body weight i.p.). The compounds such as 6b, 6a, and 6c
showed a significant percentage increase in sleeping time relative to the control experiment 423.8, 387.6 and 329.5
respectively. The preclinical evaluation of the compounds was ascertained by blood-brain barrier, human oral absorption
prediction and in silico toxicity assessment.
Keywords: Benzimidazole chalcones, DFT study, imines, hypnotic.
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