Additive Anticonvulsant Profile and Molecular Docking Analysis of 5,5′-Diphenylhydantoin Schiff Bases and Phenytoin

Abstract

Four 5,5′-diphenylhydantoin Schiff bases possessing different aromatic species (SB1–SB4) were recently synthesized and characterized using spectroscopic and electrochemical tools. The present study aimed to ascertain the anticonvulsant activity of the novel phenytoin derivatives SB1-Ph, SB2-Ph, SB3-Ph, and SB4-Ph, containing different electron-donor and electron-acceptor groups, and their possible mechanism of action. The SB2-Ph exhibited the highest potency to suppress the seizure spread with ED50 = 8.29 mg/kg, comparable to phenytoin (ED50 = 5.96 mg/kg). While SB2-Ph did not produce neurotoxicity and sedation, it decreased locomotion and stereotypy compared to control. When administered in combination, the four Schiff bases decreased the phenytoin ED50 by more than 2× and raised the protective index by more than 7× (phenytoin+SB2-Ph). The strongest correlation between in-vivo and docking study results was found for ligands’ interaction energies with kappa and delta receptors. These data, combined with the worst interaction energies of our ligands with the mu receptor, suggest that the primary mechanism of their action involves the kappa and delta receptors, where the selectivity to the kappa receptor leads to higher biological effects. Our findings suggest that the four Schiff bases might be promising candidates with potential applications as a safe and effective adjuvant in epilepsy.

Small Schiff Base Molecules—A Possible Strategy to Combat Biofilm-Related Infections

“…Due to their ease of synthesis and their wide range of applications, salicylaldehyde Schiff bases are frequently cited in the relevant literature. These compounds demonstrate antimicrobial potential, both as simple ligands and as metal complexes [56][57][58]. The antimicrobial activity is directly influenced by substitutions on the salicyl moiety, with halogenation exerting a noticeable impact in particular [58].…”

“…These compounds demonstrate antimicrobial potential, both as simple ligands and as metal complexes [56][57][58]. The antimicrobial activity is directly influenced by substitutions on the salicyl moiety, with halogenation exerting a noticeable impact in particular [58].…”

“…Schiff bases have numerous applications including coordination chemistry [23], catalysis [24], chemosensors [25] and intermediates in synthesis [26,27]. They also exhibit a variety of biological applications: antibacterial [28][29][30][31][32][33][34], antifungal [34][35][36], antiviral [37,38], antimalarial [39,40], antituberculosis [41][42][43], anthelmintic [44,45], urease inhibitors [46][47][48], anticancer [49][50][51], antidyslipidemic [52], antidiabetic [53,54], antidepressant [55][56][57], anticonvulsant [58,59], neurodegenerative disorder treatment [60,61], anti-inflammatory [62] and antioxidant [53,54].…”

Recent advances on the DNA interaction properties of Schiff bases and their metal complexes

“…13 Many SBs are known to be used in a broad range of fields, including electroluminescence, 14-17 luminescence, [18][19][20] energy materials, 21 analytical chemistry, 22 food industry, 23 catalysis, [24][25][26] dye industries, 27,28 manufacturing of polymer-based substances, 29,30 use as detectors, [31][32][33] organic optoelectronic substances, 34,35 and pharmacological agents. 36 Pharmacological applications include anti-inflammatory, 37,38 antitumor, 39,40 anti-convulsant, [41][42][43][44] anti-fungal, 44-46 painkillers, 47 anti-bacterial, [48][49][50] anti-malarial, 51,52 antiviral, [53][54][55][56][57] anti-helminthic, 58,59 anti-oxidants, [60][61][62] and DNA interaction 63 and further along (Scheme 2). Because of their DNA-binding characteristics, SB metal complexes have garnered significant interest over the past 10 years.…”