Murrayanine-hydantoin and -thiohydantoin analogs as promising anti-convulsant agents: synthesis, characterization and molecular docking studies

Abstract

Based on the fact that three scaffolds; viz. murrayanine, Schiff's base, and hydantoin have been reported to exhibit potent anti-convulsant activity, therefore, all three of them were integrated to shape a hybrid molecule which is believed to demonstrate excellent anti-convulsant activity owing to the incorporation of scaffolds. The present research involved rational designing of anti-convulsant agents having murrayanine scaffold linked with hydantoin moiety via Schiff's base linkage with an objective that the analogs will demonstrate enhanced anti-convulsant activity than their parents and also show comparable activity with the standard drug. The anti-convulsant activity was screened at dose levels of 30, 100, and 300 mg/kg utilizing maximal electroshock-induced seizure (MES) threshold test where molecule (5) displayed the most potent activity at doses 30 mg/kg (0.5 hr) and 100 mg/kg (4 hr), respectively, with comparison to the standard drug, phenytoin. In contrast, the compound (8) compound exhibited activity at 100 mg/kg (0.5 hr) and 300 mg/ kg (4 hr), respectively in male Albino Swiss mice. The research revealed the prospective of murrayanine-Schiff's base-hydantoin derivatives as active anti-convulsant activity. The characterization data were found to be in full agreement with the structural aspects. The molecular docking study revealed the possible interaction of the ligands with the NaVAb voltage-gated sodium channel, thereby proving the possible mechanism of molecule action. This study will certainly promote researchers in the rational synthesis of hybrid molecules with pronounced anti-epileptic activity.

Highly efficient microwave synthesis of rhodanine and 2-thiohydantoin derivatives and determination of relationships between their chemical structures and antibacterial activity

“…12 The presence of these double-bonded atoms with other functional groups results in particularly high density of binding sites for polar interactions and hydrogen bonds, which are responsible for their interesting biological properties. 13 A spectrum of their biological activity includes antifungal, 14,15 anticancer, [16][17][18] antidiabetic, 19,20 anti-inammatory, 21 antiviral, 22,23 anticonvulsant [24][25][26] and enzyme-inhibiting properties. 27,28 Another noteworthy feature of such cyclic systems is their strong polar and electron-withdrawing character, making them popular anchoring and electron-accepting groups in construction of merocyanine dyes for organic dye-sensitized solar cells (DSSC).…”

Edema reducing potentials of some emerging Schiff’s bases of murrayanine

“…1 Till date, the ethnopharmacological importance of the root, stem bark, and leaves are known successfully such as purgative, anthelminthic, febrifuge, carminative, astringent, and stomachic. 2 In our previous research done so far, benzothiazepine, 3 oxadiazole, 4 3,4-methylenedioxy, 5 thiazole, 6 benzoxazepine, 7 thiadiazole, 8 isoxazole, 9 hydantoin, 10 phthalimide, 11 pyrimidine, 12 benzodiazepine, 13 pyrazole, 14 chalcone, 15 and methylsulfone 16 derivatives of murryanine have been rationally synthesized as hybrids in our laboratory, characterized comprehensively, and biologically screened in various animal models to explore their pharmacological potentials such as anti-convulsant, anti-inflammatory, anti-anxiety, anti-diabetic, anti-oxidant, anti-fungal, and anti-bacterial.…”

Exploring the site‒specific influence of hydroxyl group in ring‒B of murrayanine‒chalcone on edema reducing potential

“…3 Murrayanine is the most imperative, most active, and highly explored phytoconstituent which have been studied by our research group over the years. 4 A chalcone derivative, designated by us as "Murrayanine-Chalcone" was synthesized, 5 and a number of heterocyclic derivatives (oxadiazole, 6 thiazole, 7 thiadiazole, 8 hydantoin, 9 benzodiazepine, 10 pyrazole, 11 benzoxazepine, 12 pyrimidine, 13 benzothiazepine, 14 isoxazole, 15 3,4-methylenedioxy, 16 and phthalimide, 17 were fabricated in order to amplify the biological activities (anti-diabetic, anti-inflammatory, anti-oxidant, anti-anxiety, antibacterial, anticonvulsant, and anti-fungal) by using the most common strategy 'hybridization'. Chalcone or 1,3-diphenyl-2E-propene-1-one comprises of a benzylideneacetophenone scaffold where the two aromatic nuclei joined by a three carbon α, β unsaturated carbonyl bridge.…”