In this study different derivatives of ferrocene-incorporated acyl ureas and homoleptic cadmium carboxylates were investigated for potential anticonvulsant, anxiolytic and sedative properties, using in-silico and in-vivo techniques. The molecular docking studies reveled that ferrocene compounds derivative 1-(4-bromobenzoyl)-3-(4-ferrocenylphenyl) urea (PB1) and cadmium compounds derivative bis (diphenylacetato) cadmium (II) (DPAA) exhibit binding affinities against various neurotherapeutic molecular targets involved in epilepsy, anxiety, and sedation. Both PB1 and DPAA showed high binding affinities against protein targets like mammalian shaker voltage dependent potassium channel beta subunit complex, calcium release-activated calcium channel, sodium channel 2A inactivation gate, human sodium/hydrogen exchanger regulatory factor, and gamma amino butyric acid A receptor associated protein. PB1 (2-10 mg/kg) and DPAA (1-5 mg/kg) delayed onset time of pentylenetetrazole-induced myoclonic jerks and tonic-clonic seizures in mice while decreased duration of tonic-clonic seizures, determining the anticonvulsant effect of these compounds. PB1 and DPAA (0.5-1 mg/kg) exhibited anxiolytic effect by increasing time spent and number of animals entries into open arms, while decreasing time spent in dark compartment. Furthermore, PB1 (0.5-1 mg/kg) and DPAA (0.1-1 mg/kg) reduced onset time of sleep and increased duration time of sleep in mice, showing sedative effect. Taken together, our results indicate that aforementioned derivatives of ferrocene and cadmium are potent neurotherapeutic agents possessing anticonvulsant, anxiolytic and sedative properties.
Keywords: anticonvulsant; anxiolytic; ferrocene-incorporated acyl ureas; homoleptic cadmium carboxylates; molecular docking; sedative.
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