Synthesis and Anticonvulsant Activity of Various Mannich and Schiff Bases of 1,5-Benzodiazepines

Abstract

Benzodiazepines have a various behavioral effects in addition to their anxiolytic action. There is every reason to believe that the BZ/GABA receptor complex is involved in these effects, since GABAmimetic manipulations modify the effect of BZ in tests of convulsive activity, motor function, and appetitive behavior. 1,5-Benzodiazepines are biologically important molecules and are extensively used clinically as analgesic, hypnotic, sedative, and antidepressive agents. Hence, 1,5-Benzodiazepines were synthesized by condensation of o-phenylenediamine and ketones, for example, cyclohexanone and acetone in presence of sulfated zirconia (catalyst). Mannich bases were synthesized with acetophenone, p-nitroacetophenone, p-chloroacetophenone, and formaldehyde. Schiff bases were synthesized using Mannich base of 1,5-benzodiazepines with p-chloroaniline and p-chlorophenylsemicarbazide in the presence of glacial acetic acid. All the synthesized compounds were characterized by 1H NMR and IR spectral analyses. All the synthesized derivatives were evaluated at the dose of 30 mg/kg b.w for anticonvulsant activity by isoniazid induced convulsion model, and the compounds NBZD-3 and NBZD-8 were found to be the most active among all compounds. Among all the synthesized derivatives, compounds NBZD-13 and NBZD-17 were found to be the most active among all compounds using thiosemicarbazide induced model. Although NBZD-8, NBZD-10, and NBZD-18 are the compounds which had shown good anticonvulsant activity and have an advantage over that, they were not sedative.

Mannich Bases: An Important Pharmacophore in Present Scenario

“…Among all the synthesized compounds 20a with cyclohexane at position 2 and 21a with methyl group at positions 2 and 4 were found to most active among all the synthesized compounds. The compounds 20b , 20b , and 21c were found to be least active [ 48 ].…”

Schiff Bases as Important Class of Pharmacological Agents

“…Schiff bases form an important class of the most widely used organic compounds and has a broad wide variety of applications in many fields such as biology, medicine, inorganic and analytical chemistry [3][4][5]. Schiff bases derived from various heterocyclic compounds, display broad range of biological activities such as antibacterial [6][7][8], antifungal [9], antimycobacterial [4,7], antianthrax [10], antiviral [11,12], anticancer [13], antiprotozoal [4,14], antiparasitic [15,16], anticonvulsant [17], analgesic [18], antiinflammatory [18,19], antiplatelet [20], antioxidant, antiproliferative [21], antipyretic properties [22,23], cardioprotective, antidepressant, antihypertensive, herbicidal, antiglycation and cytotoxic activity [5].…”

Antibacterial Screening of Newly Synthesized Mannich Bases Derived From 5h-Dibenzo[b,f]azepine-5-Corboxamide Against Gram Positive and Gram Negative Pathogens

“…In 1912 Germen chemist Carl Mannich antibacterial, [3][4][5] antifungal, [6][7] anticonvulsant, [8] anticancer [9] and anti-inflammatory [10] agents.…”