In silico and in vivo investigation of ferrocene‐incorporated acyl ureas and homoleptic cadmium carboxylate derivatives for anticonvulsant, anxiolytic, and sedative potential

Abstract

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.

Crystal structure and Hirshfeld surface analysis of (Z)-N-{chloro[(4-ferrocenylphenyl)imino]methyl}-4-ferrocenylaniline N,N-dimethylformamide monosolvate

“…4-Ferrocenyl aniline was synthesized using a previously described procedure (Adil et al, 2018). In a 100 ml flask, 4ferrocenyl aniline (1 mmol) and 4-ferrocenylphenyl carbonimidic dichloride (1 mmol) were dissolved in DMF (20 mL) to which potassium carbonate (2 mmol) and tetra-n-butyl ammonium bromide (0.20 mmol) were added.…”

Crystal structure and Hirshfeld surface analysis study of (E)-1-(4-chlorophenyl)-N-(4-ferrocenylphenyl)methanimine

“…Compounds containing metallocene building units, and particularly ferrocene derivatives, have been studied extensively both in academic and industrial settings (Santos et al, 2017;Singh et al, 2019;Ong & Gasser, 2020). Owing to a favorable combination of chemical and physical properties, ferrocene derivatives are often biologically active, making them attractive pharmacophores for drug design and useful templates in medicinal chemistry research and therapeutic applications including as antioxidant (Bugarinović et al, 2018;Naz et al, 2020), anti-inflammatory (Yun Guo et al, 2019), antimalarial (Peter & Aderibigbe, 2019;Xiao et al, 2020), antileishmanial (Rauf et al, 2016), anticancer (Wang et al, 2020;Ismail et al, 2020), antiplasmodial (García- Barrantes et al, 2013), anticonvulsant (Adil et al, 2018) and antimicrobial (Damljanović et al, 2009) agents. A wide range of therapeutic activities is also associated with ferrocenyl Schiff bases, which have shown exceptionally high activities against pathogenic microbes (Chohan & Praveen, 2000;Chohan et al 2001), and these molecules exhibit potent antioxidant and DNAprotecting properties (Li & Liu, 2011).…”

Synthesis, characterization, molecular docking evaluation, antidepressant, and anti‐Alzheimer effects of dibenzylidene ketone derivatives

“…Acute toxicity test of the dibenzylidene ketone derivatives is carried out according to the previously determined procedure (Adil et al, 2018;Chen et al, 2009). Mice were kept on overnight fasting and divided into four groups with each containing five animals.…”