Synthesis and anticonvulsant activities of novel 2-(cyclopentylmethylene)hydrazinyl-1,3-thiazoles in mouse models of seizures

Abstract

Synthesis, characterization and investigation of in vivo anticonvulsant activities of 13 novel cyclopentanecarbaldehyde-based 2,4-disubstituted 1,3-thiazoles are presented. Their structures were determined using 1 H and 13 C NMR, FAB(+)-MS, HRMS and elemental analyses. The results of anticonvulsant screening reveal that seven intraperitoneally administered compounds: 3a, 3b, 3d, 3e, 3f, 3k and 3m containing F-, Cl-, Br-, CF 3 -, CH 3 -and adamantyl substituents demonstrated significant anticonvulsant activity in the pentylenetetrazole model with median effective doses (ED 50 ) 20 mg/kg, respectively, which was approximately seven-fold lower than that reported for the reference drug, ethosuximide. Noteworthy, none of these compounds impaired animals' motor skills in the rotarod test.

Molecular Structure, DFT, Vibrational Spectra with Fluorescence Effect, Hirshfeld Surface, Docking Simulation and Antioxidant Activity of Thiazole Derivative

“…Thiazole is one of the most important class of heterocyclic rings bearing sulphur and nitrogen atoms . Its fusion with other moieties has proved its meticulous position in chemistry and drugs fields, because of its potential biological activities exhibited with lesser side effects, such as antimicrobial, anticonvulsant, antibacterial, anticancer, and antioxidant properties. Especially, antioxidant is one of the familiar biological property shown by thiazole derivatives and are highly conspicuous with its biological relevance.…”

Ultrasound Aided Expedient Synthesis, Characterization and Antimicrobial Studies of Fluorenyl-Hydrazono-Thiazole Derivatives

“…In addition to vitamin B1 (thiamine), the thiazole ring is found in many potent biologically active agents such as penicillins (antibacterial drugs), sulfathiazole (antimicrobial drug), ritonavir (antiretroviral drug) and meloxicam (anti-inflammatory drug). Compounds containing thiazole moiety have been reported to manifest wide spectrum of biological activities such as for treatment of allergies [1], hypertension [2], inflammation [3], schizophrenia [4], HIV infection [5,6], tumour [7][8][9] and convulsions [10][11][12]. The scrutiny for new biologically active analogues continues to be a zone of intensive research in medicinal chemistry [13,14].…”

Synthesis, antimicrobial and anticonvulsant screening of small library of tetrahydro-2H-thiopyran-4-yl based thiazoles and selenazoles

“…Importantly, this process strongly relies on the implementation of preclinical animal models before anticonvulsant active agents are assessed in clinical trials 9,51 . Our earlier studies have shown that compounds containing -F, -Cl and -CH 3 substituents demonstrated significant anticonvulsant activity in pentylenetetrazole model with median effective doses (ED 50 ) 20 mg/kg 36 . Therefore, in our current research we decided to choose three thiazole and three selenazole derivatives containing -F, -Cl and -CH 3 substituents.…”

“…Keeping in mind the above facts and continuing our previous investigation on the synthesis and molecular interaction of biologically active azoles [34][35][36][37] , we decided to prepare twelve novel 2,4-disubstituted 1,3-thiazoles and ten novel 2,4-disubstituted 1,3-selenazoles containing tetrahydro-2H-thiopyran-4-yl pharmacophore to improve their biological properties and increase the possibility of their future use.…”