Amides and hydrazides of aroylpyrivic acids. Part 6 Synthesis and study of antiinflammatory and analgesic activity of β-aroylpyruvoyl hydrazides of 2-methyl(phenyl)-4-quinolinecarboxylic acids

Abstract

Previously we have demonstrated that 4-quinolinecarboxylic acid amides and hydrazides, substituted at position 2, exhibit pronounced antiinflammatory and analgesic activity at a quite low toxicity [1 -5]. It was established that the charaeter and strength of the pharmacological action depend on the type of substituents at positions 2 and 4 of the quinoline cycle.As is known, introduction of the aroylpyruvoyl fragment into amides and hydrazides imparts to them a high antiinflammatory and analgesic activity [6,7]. In this connection, we have synthesized cinehoninie acid hydrazides containing aroylpyruvoyl fragments at the 15-nitrogen atom. The new compounds, namely, 13-aroylpyruvoyl hydrazides of 2-methyl-(I) and 2-phenyl-4-quinolinecarboxylic (II) acids were obtained using a reaction of 5-aryl-2,3-dihydro-2,3-furandiones with 2-methyl-and 2-phenyl-4-quinolinecarboxylic acids according to the scheme.Compounds I and II appear as white crystalline substances (except for Ih) poorly soluble in ethanol, benzene, chloroform, and acetonitrile, and soluble in DMSO and DMF. Their structures were established using the data of elemental analyses and the results of IR and IH NMR spectroscopic measurements. Similarly to the other pyruvic acid derivatives, the synthesized compounds provide red coloration of an ethanol solution of iron(Ill) chloride, which is evidence for the presence ofenolic hydroxyl [9,10].The IH NMR spectra of compounds Ia-Ih, IIb, and IIe contain signals attributed to the protons of methyl group (2.28-2.71 ppm), methoxy group (3.65-3.75ppm), and methine group (6.83-7.21 ppm), and a group of signals belonging to the protons of benzene ring and quinoline cycle I For the previous communication of this series see [1].

Study on synthesis, structure, and DNA-binding of Ni, Zn complexes with 2-phenylquinoline-4-carboylhydrazide

“…These endonucleolytic cleavage of DNA by metal complexes are used as models for the reactivity of some antitumor antibiotics. Previously some work demonstrated that 4-quinolinecarboxylic acid amides and hydrazides, exhibit pronounced antiinflammatory and analgesic activity at a quite low toxicity [8][9][10][11][12], but no metal complexes of such drug have been reported in the past which may have better pharmaceutical effect. Therefore, studies of the metal complexes are important to explore the possible new drug compare with the present drug.…”

Non-intercalative, Deoxyribose Binding of Boric Acid to Calf Thymus DNA

“…Molarities of calf thymus DNA solutions were confirmed by spectrophotometric analysis (assuming ε 260 =6,600 M −1 cm −1 [16]). The ratio of absorbance at 260 and 280 nm was determined to verify solution purity, and a ratio between 1.7 and 2.0 was taken to indicate that the DNA samples were satisfactorily free of protein [17][18][19][20].…”

Synthesis, characterization, and DNA-binding properties of copper(II), cobalt(II), and nickel(II) complexes with salicylaldehyde 2-phenylquinoline-4-carboylhydrazone

“…The coordination compounds of aroylhydrazones have been reported to act as enzyme inhibitors [13] and are useful due to their pharmacological applications [14][15][16]. Previously, some work demonstrated that 4-quinolinecarboxylic acid amides and hydrazides, substituted at position 2, exhibit pronounced anti-inflammatory and analgesic activity at a quite low toxicity [17][18][19][20][21], but no metal complexes of such drugs have been reported in the past which might possibly have better pharmaceutical effect. Therefore, studies of the metal complexes are important in the search for new drugs.…”