Synthesis and antimicrobial activity of 2-phenyl-3-{1-cyclopropyl-6-fluoro-7-[4-methylpiperazin-1-yl]-4-quinolone}carboxamido-3-thiazolidin-4-ones

Abstract

The title compounds VIa -j have been prepared from the lead molecule 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid I. The lead molecule was converted to hydrazide III via acid chloride II, which on reaction with different substituted aromatic aldehydes a -j afforded Schiff base, and on further structural variation of the Schiff base furnished the final compounds VIa -j (Scheme I).The synthesized compounds were tested for their antibacterial and antifungal activity (MIC) in vitro against two Gram-positive bacteria, S. aureus and S. pyogenes, and two Gram-negative bacteria E. coli and P. aeruginosa, and fungi C. albicans, A. niger, and A. clavatus, taking gentamycin, ampicillin, chloramphenicol, ciprofloxacin, norfloxacin, nystatin, and griseofulvin as standard drugs. All the synthesized compounds have been established by elemental analysis amd IR and NMR spectral data. Quinolones are extensively investigated as broad spectrum antibacterial [1, 2], antidiabetic [3], anticancer [4], antiviral [5], and anti-HIV [6] agents. Thiazolidinones possess antibacterial [7], antiinflammatory [8], antitubercular [9], anticancer [10], antitumor [11], anti HIV [12], antifungal [13], anesthetic [14], anti-viral [15], anticonvulsant [16], diuretic [17], nematicidal [18], and antihistaminic [19] activity.We have also synthesized some amide derivatives [20 -22] of quinolones and tested their activity. We observed that some of the compounds were potent and hence we initiated this work with a Schiff base and tried to synthesize more potent antimicrobial agents in addition to thiazolidinone with priority at C-3 and N-methylpiperazine at C-7.The 1 H NMR spectra of the lead molecule contained signals from the -OH of carboxylic acid at 13.59, a multiplet signal from N-CH proton at 3.77 -3.87, a multiplet signal from the cylcopropane proton at 0.85 -1.42, and peaks for three protons of the quinolone ring at 7.98 -8.84. These signals remained similar during further structural variation at C-3 and C-7 of the quinolone ring, with disappearance of the carboxylic acid group peak. The 1 H NMR of the hydrazide contained two singlet for NH at 8.64 and NH 2 at 5.72. The Schiff base contained signals for the -CH-proton at 5.13 -7.73 and a singlet for CONH similar to hydrazide. A multiplet at 2.77 -3.20 for the piperazin-1-yl group and a singlet for >N-CH 3 at 1.87 -1.95 were also observed; a singlet at 3.27 -4.07 for -CH 2 -and 5.67 -6.20 for the proton at C-2 of the cyclized thiazolidinone containing the aromatic ring at 7.67 for -OH was also observed.The IR spectra of the lead molecule contained absorption bands for >C=O of the quinolone ring at 1747 cm -1 , for carboxylic acid at 1725 cm -1 , and 2856 -2960 cm -1 for the cyclopropyl group. A band for the amide of the hydrazide at 1622 cm -1 and for the Schiff base for >N=CH-at 1615 cm -1 band were observed. In addition to the piperazine-1-yl group, an absorption band was observed at 1031 -1047 cm -1 for N-CH; for the thiazolidinone derivatives, the absorption ban...

Antimicrobial Effect of Oligomeric Copper(ii) Derivatives of Bis(pyrimidin-2-Ylthio)- And Bis(4,6-Dimethylpyrimidin-2-Ylthio)alkanes

“…The resultant MICs for the antimicrobial effect of complexes 1-3 demonstrate that they are powerfully active, similarly to other copper(II) compounds (Patel and Patel, 2009;Despaigne et al, 2012;Recio Despaigne et al, 2012;Patel and Patidar, 2014;Mehta et al, 2015). In addition, the MIC of these complexes in g mL -1 (1.86 to 10.06) embraces several drugs such as Gentamincin and Pleuromutilin derivatives which have shown inhibition against S. aureus and E. coli within the range of 0.5 to 64  g mL -1 (Islambulchilar et al, 2011;Shang et al, 2014).…”

Antimicrobial Effect of Oligomeric Copper(ii) Derivatives of Bis(pyrimidin-2-Ylthio)- And Bis(4,6-Dimethylpyrimidin-2-Ylthio)alkanes

“…The resultant MICs for the antimicrobial effect of complexes 1-3 demonstrate that they are powerfully active, similarly to other copper(II) compounds (Patel and Patel, 2009;Despaigne et al, 2012;Recio Despaigne et al, 2012;Patel and Patidar, 2014;Mehta et al, 2015). In addition, the MIC of these complexes in g mL -1 (1.86 to 10.06) embraces several drugs such as Gentamincin and Pleuromutilin derivatives which have shown inhibition against S. aureus and E. coli within the range of 0.5 to 64  g mL -1 (Islambulchilar et al, 2011;Shang et al, 2014).…”

Bioactive fluorenes. Part III: 2,7-dichloro-9H-fluorene-based thiazolidinone and azetidinone analogues as anticancer and antimicrobial against multidrug resistant strains agents

“…Moreover, 4-thiazolidinone and its derivatives have considerable attention for the last decades due to their pharmacological potential. These derivatives are known to acquire several promising chemotherapeutical activities such as antihistaminic [15], anti-inflammatory [16], hypolipidaemic [17], antimicrobial [18], anticonvulsant and antipsychotic [19], antimalarial [20], and anti-cancer [21] activities. Numerous drugs containing thiazole or 4-thiazolidinone moieties in their structure used in broad range in the pharmaceutical market such as Niridazole, Abafungin, Fanetinole, Ralitoline and Etozoline (Fig.…”