Synthesis and biological evaluations of enoxacin carboxamide derivatives

Abstract

The present work deals with the synthesis of various enoxacin analogues via nucleophilic substitution of 3-carboxylic acid moiety of the drug by aromatic amines. The free carboxylic group was utilized in the formation of amides and the effect of functional group exchange on different biological activities of the parent was evaluated. The structure of these derivatives was established by various spectroscopic techniques and mass spectrometry. The derivatives were evaluated as antibacterial agents against a series of Gram-positive and Gram-negative bacteria whereby some of them displayed considerably improved antimicrobial profile against Gram-negative test strains. Additionally unlike enoxacin, the derivatives were also found to modulate oxidative burst response of phagocytes exhibiting moderate to significant inhibitory activity.

Identification of anti-inflammatory and other biological activities of 3-carboxamide, 3-carbohydrazide and ester derivatives of gatifloxacin

“…The ester was subjected to nucleophilic attack by adding 3 mmole methanolic solutions of aromatic amines or hydrazine respectively with continuous stirring to generate corresponding carboxamides or carbohydrazides. The reaction was processed for about 2–3 hours till completion, indicated by TLC [23]. The caroboxylates were prepared by stirring the mixture of gatifloxacin (1 gm, 2.48 mmole) and methanolic solution of alcohol or phenol derivative (3 mmole) in acidic medium at 60°C under reflux (Scheme 2).…”

“…After removal of the upper phase, neutrophils were collected and subjected to hypotonic lysis of RBC with sterile distilled water for one minute, and then washed twice with HBSS -- . Macrophages from mouse peritoneal cavity were obtained as described in our previous paper [23]. Cells were re-suspended in HBSS -- to give 1 × 10 6 /mL.…”

Searching for innovative quinolone-like scaffolds: synthesis and biological evaluation of 2,1-benzothiazine 2,2-dioxide derivatives

“…These include the cyclopropyl group at the N-1 position, the 4-methylpiperazine at C-7, and an amino moiety at C-6 as it has been demonstrated that this moiety can replace the usual fluorine in terms of activity. 42,43 As C-3 substituents, we planned to introduce groups conferring either antibacterial activity (carboxylic acid 31 and carboxamide 44,45 ) or EPI activity (ethyl ester). 25,29 To avoid the enolization of the C-4 keto group, a methyl group was introduced at the C-3 position in some derivatives.…”

New Improved Quinlone Derivatives Against Infection

“…It is evident from literature that most of the research on quinolone is directed towards group modification of the C-7 basic group of the quinolone and the effect of substitution at C-3 position of quinolones has not been studied to a large extent to produce new agents with better antimicrobial profile. Accordingly to explore the potential of 3-carboxylic quinolone derivatives as anti Gram positive and Gram negative agents, we have recently reported some novel enoxacin (Saeed Arayne et al, 2009) , levofloxacin (Sultana et al, 2011) and ofloxacin (Arayne et al, 2012) carboxamide analogues by introducing new functionality at C-3 position. In continuation of our research program to establish the structure-activity relationships of 3-carboxylic quinolone derivatives, we here in report some novel enoxacin analogues which have been prepared by introducing new functionality at C-3.…”