Semicarbazone – a versatile therapeutic pharmacophore for fragment based anticonvulsant drug design

Abstract

During the last fifteen years, semicarbazones have been extensively investigated for their anticonvulsant properties. 4-(4-Flurophenoxy) benzaldehyde semicarbazone (C0102862, V102862) was discovered as a lead molecule and is being developed as a potent antiepileptic drug, with maximal electroshock (MES) ED50 of i.p. 12.9 mg kg-1. In MES (oral screen), this compound has a protective index (PI = TD50/ED50 > 315) higher than carbamazepine (PI 101), phenytoin (PI > 21.6) and valproate (PI 2.17). The compound is a potent sodium channel blocker. Other semicarbazones have demonstrated activity in various chemoshock screens, like subcutaneous pentylenetetrazole, subcutaneous strychnine, subcutaneous picrotoxin and subcutaneous bicculine. Semicarbazones are also GABA-transaminase inhibitors. Extensive structure- -activity relationship has demonstrated that F, Cl, Br and NO2 substituents in the arylhydrophobic pocket and a hydrogen bonding domain (HBD) are generally found in active anticonvulsant agents.

Elucidation of Cyclic Voltammetric Behaviour of N-Hydroxy-3-Isopropyl-2,6-Difurylpiperidin-4-One Semicarbazone and Thiosemicarbazone and the Antibacterial Study of the Products

“…The positions and shapes of the peaks were dependent on the scan rate but the numbers of peaks remain same. The results were indicative of an irreversible two electron transfer to electro reduction of semicarbazone and thiosemicarbazone moiety [19][20][21][22][23][24][25] .…”

“…The product Amino(2-(N-hydroxy-3-isopropyl-2,6-difurylpiperidin-4-one-ylidene) hydrazinyl) methanol(3a) and Amino(2-(N-hydroxy-3-isopropyl-2,6-difurylpiperidin-4-oneylidene) hydrazinyl) methane thiol(3b) were screened for the antibacterial activity for eight test bacteria [21][22][23][24][25][26][27][28] . The bacterial strains used for inhibition study and the results were revealed in the table 5.…”

“…In this study a paraffin-impregnated graphite electrode was used as the working electrode. The electrochemical behavior of 0.01M N-hydroxy-3-isopropyl-2,6-difurylpiperidin-4-one semicarbazone(2a) and N-hydroxy-3-isopropyl-2,6-difurylpiperidin-4-one thiosemicarbazone(2b) were dissolved in respective mixed solvent of 0.1M of ethanol and distilled water [17][18][19][20][21][22][23][24] and it was studied with Cyclic voltammetric technique in the potential range -2100mV to 2100mV and with the variable scan rate range of (100mVs -1 ,150 mVs -1 and 200mVs -1 ). The yield of the reduced products is listed in Table 3.…”

Fluorescence of isatin N‐phenylsemicarbazones: aggregation and hydrazide–hydrazonol tautomerism

“…Despite the low fluorescence intensity of isatin N ‐phenylsemicarbazone derivatives due to the predominant non‐radiative excited state deactivation, results of this study can be a useful supplement for better understanding of complex processes in solution of effective colorimetric sensors based on isatin N ‐phenylsemicarbazone. Moreover, because isatin semicarbazones are often biologically active, concept of associate/hydrazide/hydrazonol equilibrium in solution can help other researches in this field to deeply understand the structure–property and structure–biological activity relationships of some isatin semicarbazones. Structure of studied isatin N ‐phenylsemicarbazone E ‐isomers is depicted in Scheme .…”

Solubility of a Pharmacological Intermediate Drug Isatin in Different Solvents at Various Temperatures

“…Moreover, isatins are the synthetic precursors of some biologically important compounds 14,15 . Because of the continuing interest about isatin and its derivatives [16][17][18][19] , the present work was undertaken to test the solubility of isatin in different solvents at different temperatures and as a result, to evaluate different thermodynamic parameters. Further, various thermodynamic parameters have been evaluated from these solubility data.…”