Antituberculous Isonicotinylhydrazones of Low Toxicity

Abstract

In a search for antituberculous compounds of low toxicity, the isor~icotinyl-hydrazones of monohydroxybenzalde1~ydes and of the corresponding aldehydophenoxyacetic acids were prepared. When tested in uiuo, the isonicotinylhydrazones of 2-formyl-phenosyacetic acid and of 6-methosy-2-forr>l>~l-pllenoxyacetic acid showed the most marked antituberculous activity combined with low tosicity. The preparation of 6-methoxy-2-formyl-pherloxyacetic acid and of the isonicotinylhydrazone of 2-formyl-pherloxyacetic acid are described as representative examples. The results of microanalysis include data which define the antituberculous isonicotillylhydrazo~~es of 2-hydroxybenzaldeh)~de, 4-hydroxybenzaldehyde, and 2-hydroxy-3-methoxybenzaldehyde (0-vanillin). INTRODUCTIONFollowing the discovery of the antituberculous activity of isonicotinic acid hydrazide (isoniazid) by Grunberg and Schnitzer (5) and by Bernstein et al.(1) we recorded the marlied therapeutic action in the experimental tuberculous infection in mice of isonicotinylhydrazones of hydroxy substituted benzaldehydes (8). As a representative example of this group of compounds the isonicotinylhydrazone of 4-hydroxybenzaldehyde (I) was studied more closely (7).The low toxicity in mice shown by (I), as well as by isonicotinylhydrazones of other monohydroxybenzaldehydes, encouraged us to extend our research in this field.As the in vitro antituberculous activity of (I) approaches that of isoniazid, it was considered likely that the limited in vivo activity of thiscompound, as compared to that of isoniazid, may in part be due to its low solubility. I t appeared desirable, therefore, to introduce suitable modifications in the molecular structure to render this type of co~npound more soluble. On the basis of this idea we have prepared, as starting materials for isonicotinylhydrazones, a series of aldehydo-phenoxyacetic acids, namely: 4-formyl-phenoxyacetic acid (3) from 4-hydroxybenzaldehyde, 2-formyl-phenoxyacetic acid (2, 6) from salicylaldehyde, 6-methoxy-2-formyl-phenoxyacetic acid from o-vanillin (2-hydroxy-3-meth-

Synthesis and Characterization of Schiff Base Complexes of o-Vanillin and Anthranilic Acid and Their Biological Evaluation

“…It is an interesting and fascinating member of the family of Schiff bases containing two aromatic rings with -OH group at ortho position. The amino acids on condensation with an aldehyde group has shown conserved activity upon inactivation of the -NH2 group of the parent anthranilic acid [1][2][3][4]. Different types of Schiff base ligands and their transition metal complexes have been widely studied for biological [5][6][7][8], material [9][10][11][12] and industrial applications [13,14].…”

High-performance liquid chromatographic analysis of the antituberculosis drugs aconiazide and isoniazid

“…Aconiazide (ACON), the isonicotinylhydrazone of 2-formylphenoxyacetic acid, was syn-* Corresponding author. thesized as one of several antituberculosis isonicotinylhydrazones [11]. ACON appears to be less toxic than INH and equally effective against M. tuberculosis [12,13].…”

Novel glitazones as PPARγ agonists: molecular design, synthesis, glucose uptake activity and 3D QSAR studies

“…Rationally designed target compounds belonging to the class of 2-(4-((substituted phenylimino)methyl)phenoxy)acetic acid; ( CPD01-24 ) were synthesized according to the Scheme 1 [28, 29]. Two aromatic aldehydes, namely, viz.…”

“…Formylphenoxyacetic acid was prepared by modifying Williamsons ether synthesis protocol [28], by taking sodium phenoxide and treating it with equivalent amounts of chloroacetic acid in presence of sodium hydroxide. The whole solution of prepared sodium phenoxide in the previous step was taken in a beaker, to that 30 ml of chloroform was added and the solution was stirred mechanically for a period of 10 min at room temperature.…”