Design and synthesis of novel cycloalkanecarboxamide parabanic acid hybrids as anticonvulsants

AbstractAiming to develop novel anticonvulsant agents a new series of novel cycloalkanecarboxamide parabanic acid hybrids series8,9 and10 possessing the essential structure requirements for anticonvulsant activity was synthesized starting from cycloalkanones. All final target compounds were primary screened for chemically and electrically induced seizures using pentylenetetrazole “scPTZ” and maximal electroshock seizure “MES” models. In phase I anticonvulsant evaluation compounds8b and10b exhibited the highest potency among all the target compounds with 100% protection towards chemically induced seizures. Results of phase II anticonvulsant screening showed that compounds8b and10b are more potent than standard drug ethosuximide by about 11 and 9 fold, respectively. Regarding MES test, compounds8b and9a-d exhibited 100% protection with ED50 values ranged between 0.107 –0.177 mmol/Kg. All final compounds did not display any signs of motor impairment in the neurotoxicity screening test. Also, compounds8a,9a-d and10b were devoid of hepatotoxicity as shown by measurement of serum levels of liver enzymes, albumin as well as total protein. Moreover, the cyclohexyl derivative10b produced a significant increase of Gamma-aminobutyric acid “GABA” brain’s content of mice compared to control group confirmed its GABAergic modulating activity. Molecular docking, physicochemical and pharmacokinetic properties were carried out for all compounds as well. These outcomes support...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research