Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues

Abstract

In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 μM.

Antinociceptive and Anti-inflammatory Activities of the Ethanolic Extract, of Fractions and of Epicatechin Isolated from the Stem Bark of Ximenia americana L. (Oleacaceae)

“…5,7-Dihydroxy arrangement in the A ring, such as present in XM-Catechin (1), increase antioxidant effects and 5-OH enhances peroxynitrite scavenging ability. 17,28,40 Free radical scavenging by flavonoids is highly dependent on the presence of a free 3-OH in the C-ring. The torsion angle of the Bring with respect to the rest of the molecule strongly influences free radical scavenging ability.…”

“…36 In this model, pro-inflammatory cytokines, such as TNF-α and IL-1β, activate the signaling pathway in endothelial cells, which regulates the expression of adhesion molecules to initiate the recruitment of both circulating leukocyte migrating cells and partially activated leukocyte cells. 28,38 when they respectively studied the antinociceptive activity of aqueous extract of stem bark and anti-inflammatory property of the aqueous ethanol extract of root bark of X. americana.…”

Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

“…The pharmacological screening revealed that compounds 1 ( a–h ) have exhibited better activity than standard drug piroxicam. Compounds 1f and 1g were identified as new anti-inflammatory and antinociceptive agents which were capable of inhibiting cell recruitment by 70% and 80%, respectively, at dose of 100 μ mol/kg, p.o in zymosan- and carrageenan-induced peritonitis [ 36 ].…”

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“…The results clearly revealed that all ten compounds possess in vitro antioxidant activity at the tested dose as compared to the standard drug, ascorbic acid as shown in Figure 11. Miranda et al [89] synthesized a chain of N-acylhydrazones41(a-h) from commercially available compound (39) ethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide in subsequent two steps, as given in Figure 12 Kaushik et al [90] synthesized a series of N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 2/4-substituted hydrazides (42). The anti-convulsant activity of the synthesized compound was analysed against maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) induced seizure modelsin mice.…”