Nicotinic acid hydrazones: a novel anticonvulsant pharmacophore

Abstract

A series of aryl acid hydrazones of substituted aromatic acid hydrazides (D 1 to D 20 ) were synthesised and evaluated for anticonvulsant activity. Aryl acid hydrazones of Nicotinic acid hydrazide (D 8 , D 9 , and D 10 ) have displayed excellent protection in maximal electroshock screen. These compounds have also exhibited excellent binding properties with Lys 329 residue of gamma amino butyrate amino transferase (GABA-AT) in Lamarckian genetic algorithm based flexible docking studies. Compound D 8 , N 1 -(4-chlorobenzylidene) nicotinohydrazide was found to be the most potent analog with ED 50 value of 16.1 mg/kg and protective index (PI = TD 50 /ED 50 ) value of [20, which was much greater than that of the prototype drug phenytoin (PI = 6.9). It has shown free binding energy value of -10.20 kcal/mol and inhibition constant (Ki) value of 33.30 nM for GABA-AT, indicating that aryl acid hydrazones of nicotinic acid hydrazide could be considered as a new pharmacophore in the design of novel anticonvulsant drugs.

The complexing properties of oxalodihydrazide, acethydrazide and formic hydrazide with Cu(II) in aqueous solution

“…Aliphatic hydrazides like oxalodihydrazide are known to inhibit protease enzymes in some parasitic species and diamine oxidases [8]. Acid hydrazones of isonicotinic acid hydrazide, a well-known tuberculosis treating agent, demonstrating a strong anticonvulsant effect, could be considered as a pharmacophore in the design of novel drugs [9].…”

Synthesis and evaluation of some novel derivatives of 2-propoxybenzylidene isonicotinohydrazide for their potential antimicrobial activity

“…In conclusion, the present paper describes the preparation and biological evaluation of a series of novel isoniazid derivatives. The synthesized compounds were characterized by suitable analytical techniques, i.e., IR, 1 H-NMR, 13 C-NMR and elemental analysis and the data obtained was in full agreement of the proposed structures. Among the synthesized derivatives, compound 2c and 2k, having a diethylamino and methylpiperazine moieties, were the most active compounds with significant biological activity.…”

“…6,7 Hydrazones are formed when hydrazines react with an aldehyde or a ketone under specific condition. Hydrazones have been reported to possess antimicrobial, 8,9 antitubercular, 10,11 antileprotic, 12 anticonvulsant, 13 analgesic, 14 anti-inflammatory, 15,16 antiplatelet, 17 anticancer 18,19 and antiviral properties. 20 Inspired by the above facts and in continuation of an ongoing research program in the field of the synthesis and antimicrobial activity of medicinally important compounds, 21-24 the synthesis and antimicrobial activity of some novel derivatives of isoniazid are reported herein.…”

Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent

“…The results of the docking runs are represented in Table V. The most active compounds from the series were analyzed for their binding properties at the GABA-AT enzyme binding site at the Lys-329 residue of GABA-AT, as described (25,26). b Direct hit; all features of the hypothesis are mapped.…”

“…The search algorithm involves the positioning of molecular conformations in the active site while the scoring function determines energetically most favourable orientation of the molecule. In this study, we have used the Molegro virtual docker 4.0 program with its piecewise linear potential (PLP) based algorithm for docking of all synthesized com-pounds in the GABA-AT binding site, which was also previously reported by many authors (25,26). We have also calculated the binding affinities of these compounds compared to standard reference compounds.…”