Skip to main content
NCBI home page
Iranian Journal of Pharmaceutical Research : IJPR logoLink to Iranian Journal of Pharmaceutical Research : IJPR
. 2011 Spring;10(2):225–231.

Synthesis and In-vitro Antibacterial Activities of Acetylanthracene and Acetylphenanthrene Derivatives of Some Fluoroquinolones

Fazel Shamsa a,*, Alireza Foroumadi b, Hashim Shamsa a, Nasrin Samadi c, Mohammad Ali Faramarzi d, Abbas Shafiee a
PMCID: PMC3828925  PMID: 24250347

Abstract

Novel analogues of N-piperazinyl fluoroquinolones were prepared and evaluated against a panel of Gram-positive and Gram-negative bacteria, to study the effect of introducing bulky anthracene and phenanthrene moieties on the antibacterial effects of norfloxacin, ciprofloxacin and gatifloxacin. Although most of the novel synthesized compounds had lower antibacterial effects, some derivatives showed better activity in comparison with mother drugs based on molar concentration; for example, the 3-acetyl phenanthrene analogue of norfloxacin was more effective than E. coli and K. pneumonia.

Key Words: N-substituted piperazinyl quinolones, Anthracene derivatives, Phenanthrene derivatives, In-vitro antibacterial activity

Introduction

Quinolones are a group of synthetic antibacterial agents structurally related to nalidixic acid (1). Nalidixic acid was the first introduced quinolone for the treatment of urinary tract infections caused by Gram-negative organisms (2, 3). Since the discovery of nalidixic acid, more than 10000 analogues have been synthesized and their antibacterial activities were evaluated (4). Fluorination of the quinolones at C-6 position and introduction of piperazine ring at C-7 position by Koga and colleagues (5) led to the evolution of fluoroquinolones, i.e. ciprofloxacin 1, norfloxacin 2, and gatifloxacin 3 (Figure 1), as new broad spectrum antibacterial drugs with better antibacterial and pharmacokinetic profiles (6). The main mechanism of these drugs is in the inhibition of DNA gyrase and topoisomerase IV (7). It was shown that DNA gyrase inhibition and the entrance into the microbial cells significantly depend on the groups of C-7 (8, 9). Some fluoroquinolone derivatives with thiophene (10, 11), furan (12), substituted phenyl (13) and coumarin (14) attached to the piperazine ring at 7-position were synthesized with better antibacterial effects against Gram-positive bacteria (Figure 1.1-1.4). Recently, the synthesis of some N-[2-(2-naphthyl)ethyl] piperazinyl quinolones (Figure 1.4, Ar = 2-naphthyl) with potent antibacterial activity against Gram-positive and Gram-negative bacteria, have been reported (15). In the present study, some novel analogues of fluoroquinolones such as ciprofloxacin 1, norfloxacin 2, and gatifloxacin 3, with 2-oxo-2-(anthracene-2-yl) ethyl (5a-c), 2-oxo-2-(anthracene-9-yl) ethyl (6a-c) and 2-oxo-2-(phenanthrene-2-yl) ethyl (7a-c) have been synthesized to study the effect of initiating bulky anthracene and phenanthrene moieties on the antibacterial activities against Gram-positive and Gram-negative bacteria.

Figure 1.

Figure 1

Open in a new tab

The change of the content of the monoterpenes and sesquiterpenes from pre-flowering to post-flowering stage

Experimental

Chemistry

All solvents and the chemicals used in this study were purchased from Merck Co. (Merck, Germany) and Aldrich chemicals agents. Melting points were determined on Electrothermal 9100 apparatus and are uncorrected. The IR spectra were obtained on a Shimadzu 470 spectrophotometer (KBr disks). 1H-NMR spectra were measured using 80 MHz spectrometer and the chemical shifts are expressed as δ (ppm) with tetramethylsilane as internal standard. Elemental analyses were within ± 0.4% of theoretical values for C, H and N.

General procedure for the peparation of 7-[4-(2-aryl-2-oxoethyl)-1-piperazinyl] quinolones 5-7

A mixture of 2-bromo-1-(anthracen-2-yl) ethanone (9a), 2-bromo-1-(anthracen-9-yl) ethanone (9b) or 2-bromo-1-(phenanthren-2-yl) ethanone (9c) (0.33 mmol), fluoroquinolone (1, 2 or 3) (0.3 mM) and NaHCO3 (0.3 mM) in DMF (5 mL), was stirred at 45°C for 48-72 h. After the consumption of fluoroquinolone, water (30 mL) was added and the precipitate was filtered, washed with water and crystallized from EtOH-CHCl3 to give the target compounds (Figure 1.5-1.7).

1-Cyclopropyl-6-fluoro-1, 4-dihydro-7-[4-[2-(anthracen-2-yl)-2-oxoethyl] piperazin-1-yl]-4-oxo-3-quinoline carboxylic acid (5a)

Yield: 60%; m.p. 163-164°C; IR (KBr, cm-1 ) υ max: 1622, 1680 and 1728 (C = O); 1H-NMR (DMSO-d6) δ : 1.12-1.33 (m, 4 H, cyclopropyl), 2.81-3.14 (m, 4 H, piperazine), 3.30-3.70 (m, 4 H, piperazine), 3.72-3.86 (m, 1 H, cyclopropyl), 4.22 (s, 2 H, COCH2), 7.29-7.60 (m, 5 H, aromatic), 7.90-8.25 (m, 4 H, aromatic), 8.45-8.70 (m, 2 H, aromatic), 8.76 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 549.1 (M+, 4), 504.3 (10), 330.4 (12), 285.2 (8), 221.2 (20), 178 (100). Anal. (C33H28FN3O4) C, H and N.

1-Cyclopropyl-6-fluoro-1, 4-dihydro-7-[4-[2-(anthracen-9-yl)-2-oxoethyl] piperazin-1-yl]-4-oxo-3-quinoline carboxylic acid (5b)

Yield: 75%; m.p. 221-223ºC; IR (KBr, cm-1 ) υ max: 1624, 1681 and 1730 (C = O); 1H-NMR (DMSO-d6) δ : 1.19-1.38 (m, 4 H, cyclopropyl), 2.81-2.93 (m, 4 H, piperazine), 3.25-3.41 (m, 4 H, piperazine), 3.60-3.90 (m, 3 H, 1 H cyclopropyl and 2 H COCH2), 7.29-7.65 (m, 5 H, aromatic), 7.96-8.20 (m, 4 H, aromatic), 8.52-8.68 (m, 2 H, aromatic), 8.72 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 549 (M+, 6), 504 (12), 330 (11), 285 (10), 221 (21), 178 (100). Anal. ( C33H28FN3O4) C, H and N.

1-Cyclopropyl-6-fluoro-1, 4-dihydro-7-[4-[2-(phenanthren-2-yl)-2-oxoethyl]piperazin-1-yl]-4-oxo-3-quinoline carboxylic acid (5c)

Yield: 40%; m.p. 278-280ºC; IR (KBr, cm-1) υ max: 1630, 1682 and 1720 (C = O); 1H-NMR (DMSO-d6) δ : 1.10-1.39 (m, 4 H, cyclopropyl), 2.81-3.10 (m, 4 H, piperazine), 3.32-3.64 (m, 4 H, piperazine), 3.72-3.84 (m, 1 H, cyclopropyl), 4.12 (s, 2 H, COCH2), 7.40-7.85 (m, 5 H, aromatic), 7.90-8.25 (m, 4 H, aromatic), 8.50-8.65 (m, 2 H, aromatic), 8.75 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 549 (M+, 4), 504 (11), 330 (12), 285 (10), 221 (22), 178 (100). Anal. (C33H28FN3O4) C, H and N.

1-Ethyl-6-fluoro-1, 4-dihydro-7-[4-[2-(anthracen-2-yl)-2-oxoethyl] piperazin-1-yl]-4-oxo-3-quinoline carboxylic acid (6a)

Yield: 65%; m.p.: 217-219 °C; IR (KBr, cm -1 ) õ max: 1624, 1685 and 1725 (C = O), 3420 (OH); 1H-NMR (DMSO-d6) ä : 1.58 (t, 3 H, CH3, J = 7 Hz), 2.55-2.71 (m, 4 H, piperazine), 3.34-3.60 (m, 4 H, piperazine), 4.12 (s, 2 H, COCH2), 4.42 (q, 2 H, CH2-CH3, J = 7Hz), 6.95 (d, 1 H, H-8 quinolone, J = 7 Hz), 7.43-7.65 (m, 5 H, aromatic), 7.97-8.30 (m, 4H, aromatic), 8.41-8.60 (m, 1 H, aromatic), 8.76 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 537 (M+, 6), 492 (8), 317 (13), 272 (9), 221 (21), 178 (100). Anal. (C32H28FN3O4) C, H and N.

1-Ethyl-6-fluoro-1, 4-dihydro-7-[4-[2-(anthracen-9-yl)-2-oxoethyl] piperazin-1-yl]-4-oxo-3-quinoline carboxylic acid (6b)

Yield: 50%; m.p.: 173-175ºC; IR (KBr, cm -1 ) õ max: 1621, 1685 and 1724 (C = O), 3420 (OH); 1H-NMR (DMSO-d6) ä : 1.60 (t, 3 H, CH3), 2.90-3.20 (m, 4 H, piperazine), 3.40-3.65 (m, 4 H, piperazine), 4.02 (s, 2 H, COCH2), 4.35 (q, 2 H, CH2-CH3), 6.90 (d, 1 H, H-8 quinolone, J = 7Hz), 7.35-7.65 (m, 5 H, aromatic), 7.70-8.20 (m, 4 H, aromatic), 8.01-8.15 (m, 1 H, aromatic), 8.72 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 537 (M+, 7), 492 (10), 317 (8), 272 (10), 221 (24), 178 (100). Anal. (C32H28FN3O4) C, H and N.

1-Ethyl-6-fluoro-1,4-dihydro-7-[4-[2-(phenanthren-2-yl)-2-oxoethyl]piperazin-1-yl]-4-oxo-3-quinoline carboxylic acid (6c)

Yield: 50%; m.p.: 173-175°C; IR (KBr, cm -1 ) õ max: 1621, 1685 and 1724 (C = O), 3420 (OH); 1 H NMR (DMSO-d6) ä : 1.58 (t, 3 H, CH3), 2.85-3.10 (m, 4 H, piperazine), 3.35-3.61 (m, 4 H, piperazine), 4.15 (s, 2 H, COCH2), 4.32 (q, 2 H, CH2-CH3), 6.85 (d, 1 H, H-8 quinolone, J = 7 Hz), 7.40-7.85 (m, 4 H, aromatic), 7.90-8.25 (m, 4 H, aromatic), 8.50-8.65 (m, 2 H, aromatic), 8.75 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 537 (M+, 7), 492 (10), 317 (8), 272 (10), 221 (24), 178 (100). Anal. (C32H28FN3O4) C, H and N.

1-Cyclopropyl-6-fluoro-7-[4-[2-(anthracen-2-yl)-2-oxoethyl] piperazin-1-yl]-8-methoxy-4-oxo-3-quinoline carboxylic acid (7a )

Yield: 54%; m.p. 183-184°C; IR (KBr, cm-1 ) υ max: 1623, 1682 and 1732 (C = O); 1H-NMR (DMSO-d6) δ : 1.02 –1.60 (m, 7H, 4H cyclopropyl and 3H CH3-piperazine), 3.30-3.70 (m, 8 H, 7 H piperazine and 1 H cyclopropyl), 3.74 (s, 3 H, CH3O), 4.12 (s, 2 H, COCH2), 7.30-7.60 (m, 5 H, aromatic), 7.88-8.22 (m, 4 H, aromatic), 8.42-8.71 (m, 1 H, aromatic), 8.83 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 593 (M+, 3), 548 (6), 372 (16), 327 (10), 221 (22), 178 (100). Anal. (C35H32FN3O5) C, H and N.

1-Cyclopropyl-6-fluoro-7-[4-[2-(anthracen-9-yl)-2-oxoethyl] piperazin-1-yl]--8-methoxy-4-oxo-3-quinoline carboxylic acid (7b )

Yield: 45%; m.p. 191-192°C; IR (KBr, cm-1 ) υ max: 1624, 1680 and 1725 (C = O); 1HNMR (DMSO-d6) δ : 0.95 –1.40 (m, 7 H, 4 H cyclopropyl and 3 H CH3-piperazine), 2.90-3.30 (m, 4 H, piperazine), 3.30-3.65 (m, 4 H, 3H piperazine and 1 H cyclopropyl), 3.79 (s, 3 H, CH3O), 4.02 (s, 2 H, COCH2), 7.52-7.55 (m, 5 H, aromatic), 8.00-8.30 (m, 4 H, aromatic), 8.50-8.63 (m, 1 H, aromatic), 8.76 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 593 (M+, 5), 548 (10), 371 (11), 327 (8), 221 (20), 178 (100). Anal. (C35H32FN3O5) C, H and N.

1-Cyclopropyl-6-fluoro-7-[4-[2- (phenanthren-2-yl)-2-oxoethyl] piperazin-1-yl]--8-methoxy-4-oxo-3-quinoline carboxylic acid (7c )

Yield: 43%; m.p. 203-204 °C; IR (KBr, cm-1 ) υ max: 1620, 1681 and 1720 (C = O); 1H-NMR (DMSO-d6) δ : 1.00 –1.65 (m, 7 H, 4 H cyclopropyl and 3 H CH3-piperazine), 3.33-3.73 (m, 8 H, 7 H piperazine and 1 H cyclopropyl), 3.75 (s, 3 H, CH3O), 4.11 (s, 2 H, COCH2), 7.40-7.85 (m, 4 H, aromatic), 7.90-8.25 (m, 4 H, aromatic), 8.50-8.65 (m, 2 H, aromatic), 8.75 (s, 1 H, H-2 quinolone). MS: m/z (rel. Int. %): 593 (M+, 5), 548 (6), 371 (10), 327 (13), 221 (30), 178 (100). Anal. (C35H32FN3O5) C, H and N.

Determination of the minimum inhibitory concentration (MIC)

The MIC of the synthesized compounds (1a-3c) were determined by conventional agar dilution method (16, 17) with respect to different microorganism test including G-positive (S. aureus ATCC 6538p, S. epidermidis ATCC 12228, and Bacillus subtilis ATCC 6633) and G-negative (E. coli ATCC 8739, K. pneumonia ATCC 10031 and P. aeruginosa ATCC 9027) bacteria. Antimicrobial activities of compounds (1a-3c) were also examined against two clinical isolate methicillin-resistant S. aureus (MRSA I and II) in addition to the mentioned microorganism test. Two-fold dilution of the test compounds and the standard antibacterial agents, 1, 2, and 3 (Figure 1) were prepared in dimethyl sulfoxide (DMSO; 1 mL). Each dilute was added to molten Mueller-Hinton (MH) agar (19 mL) at 50°C to give a final concentration of 100, 50, 25, 12.5, 6.25, 3.125, 1.56, 0.78, 0.39, 0.195, 0.098, 0.049, 0.025, 0.012, 0.006 and 0.003 μg mL-1. The bacterial inocula were prepared by suspending overnight colonies from MH agar media in 0.85% saline. The inocula were adjusted photometrically at 600 nm to a cell density equivalent to approximately 0.5 McFarland standards (1.5 x 108 CFU/mL). The suspensions were then diluted in 0.85% saline to make 107 CFU/mL. The plates were spot-inoculated with 1 μL of bacterial suspensions (104 CFU/spot); including a control plate containing 1 mL DMSO without any antibacterial agent. The plates were incubated at 35-37°C and examined after 18 h. The MIC was determined as the lowest concentration of the agent that completely inhibits visible growth of the microorganisms.

Results and Discussion

The synthetic pathways to the intermediates (9a-c) and the target compounds (5-7) are presented in Figure 2 and 3. The acetyl derivatives of anthracene and phenanthrene (8a-c) were brominated with CuBr2 in refluxing CHCl3-EtOAc to give the corresponding α-bromoacetyl derivatives (9a-c). Reactions of fluoroquinolones 1-3 with compounds 9a, 9b or 9c in DMF in the presence of NaHCO3 at 45°C afforded corresponding 7-[4-(2-aryl-2-oxoethyl)-1-piperazinyl] quinolones 5-7. Compounds 5-7 (a-c) were tested against some gram-positive (Staphylococcus aureus ATCC 6538P, Staphylococcus epidermedis ATCC 12228, Bacillus subtlis ATCC 66339) and Gram-negative bacteria (Escherichia coli ATCC 8739, K. pneumoniae 10031 and Pseudomonas aeruginosa ATCC 9027) using conventional agar-dilution method.

Figure 2.

Figure 2

Open in a new tab

Synthesis of the intermediate compounds 9a-c

Figure 3.

Figure 3

Open in a new tab

Synthesis of target compounds 5-7

The MIC (minimum inhibitory concentration) values were determined in comparison with the corresponding mother drugs (Table 1.). Through this table, it is concluded that the most sensitive bacteria is K. pneumonia which is inhibited by 1 (0.003 μg μg/mL), 2 (0.024 μg/mL) or 3 (0.006 μg/mL) and all synthesized compounds showed a good activity against this bacteria (MIC = 0.006-0.781μg mL-1). All target compounds 5-7, except compound for 5a, did not show good activity against P. aeruginosa. In most cases, the new synthesized compounds showed higher MIC values than the corresponding mother drugs against Gram-positive and Gram-negative bacteria; however, different activity profiles were observed among target compounds 5-7. Although most of the novel synthesized compounds had lower antibacterial effects, some derivatives showed better activity in comparison with the mother drugs based on molar concentration; for example, the 3-acetyl phenanthrene analogue of norfloxacin (6b) was more effective than E. coli and K. pneumonia.

Table 1.

Minimum inhibitory concentration (MIC μgmL-1) of ciprofloxacin, norfloxacin, gatifloxacin and compounds 5-7 (a-c) against some common bacteria by agar dilution method

Microorganisms
Compound S.aureus E.coli P.aeruginosa K.pneumoniae B.subtilis S.epidermidis MRSA3
Ciprofloxacin (1) 0.195 0.012 0.0391 0.003 0.195 0.195 0.391
5a 0.391 0.049 0.781 0.012 0.391 0.391 1.563
5b 3.125 1.563 12.5 0.195 3.125 6.25 6.25
5c 0.391 0.049 3.125 0.006 0.391 0.391 6.25
Norfloxacin (2) 0.391 0.049 0.781 0.024 0.391 0.781 0.781
6a 6.25 0.195 12.5 0.049 1.563 3.125 >100
6b 1.563 0.195 6.25 0.024 1.563 1.563 3.125
6c 0.781 0.049 3.125 0.024 1.563 1.563 25
Gatifloxacin (3) 0.049 0.024 0.781 0.006 0.049 0.049 0.098
7a 0.195 1.563 100 0.098 0.195 0.098 3.125
7b 0.781 3.125 100 0.781 0.781 1.563 12.5
7c 0.098 0.781 50 0.049 0.391 0.098 3.125
Open in a new tab

In conclusion, the initiation of bulky anthracene and phenanthrene moieties on piperazine ring at C-7 position of fluoroquinolones reduced the antibacterial activities against both gram-negative and gram-positive bacteria.

Acknowledgment

We acknowledge the Research Council of Tehran University of Medical Sciences and the Iranian National Science Foundation which supported this study through a grant.

References

  • 1.Andriole VT. Quinolones. In: Mandell GL, Benett JE, Dolin R, editors. Principles and Practice of Infectious Disease. 3rd ed. New York : Churchill Livingstone Inc; 1990. pp. 334–345. [Google Scholar]
  • 2.Lescher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP. 1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents. J. Med. Pharm. Chem. 1962;91:1063–1065. doi: 10.1021/jm01240a021. [DOI] [PubMed] [Google Scholar]
  • 3.Emami S, Shafiee A, Foroumadi A. Quinolones: recent structural and clinical developments. Iranian J. Pharm. Res. 2005;3:123–136. [Google Scholar]
  • 4.Higgins PG, Fluit AC, Schmitz FJ. Fluoroquinolones: structure and target sites. Current Drugs Targets. 2003;4:181–190. doi: 10.2174/1389450033346920. [DOI] [PubMed] [Google Scholar]
  • 5.Koga H, Itoh A, Murayama S, Suzue S, Lrikura T. Structure-activity relationship of anti-bacterial 6,7- and 7,8-disubstituted 1-alkyl-1,4-dihydro-4-oxoquinolone-3-carboxylic acids. J. Med. Chem. 1980;23:1358–1363. doi: 10.1021/jm00186a014. [DOI] [PubMed] [Google Scholar]
  • 6.Emami S, Shafiee A, Foroumadi A. Structural feature of new quinolones and relationship to antibacterial activity against Gram-positive bacteria. Mini- Reviews in Medicinal Chemistry. 2006;6:375–386. doi: 10.2174/138955706776361493. [DOI] [PubMed] [Google Scholar]
  • 7.Domagala JM, Hanna LD, Heifetz CL Hutt MP, Mich TF, Sanchez JP, Solomon M. New structure activity relationship of the quinolone antibacterial using the target enzyme. J. Med. Chem. 1986;29:394–404. doi: 10.1021/jm00153a015. [DOI] [PubMed] [Google Scholar]
  • 8.Shen LL, Mitscher LA, Sharma PN O’ Donnell TJ, Chu DWT, Copper CS, Rosen T. Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug-DNA binding model. Biochemistry. 1989;28:3886–3894. doi: 10.1021/bi00435a039. [DOI] [PubMed] [Google Scholar]
  • 9.Cooper CS, Klock PL, Chu DT, Hardy DJ, Swanson RN, Plattner JJ. Preparation and in-vitro and in-vivo evaluation of quinolones with selective activity against gram-positive organism. J. Med. Chem. 1992;35:1392–8. doi: 10.1021/jm00086a007. [DOI] [PubMed] [Google Scholar]
  • 10.Shafiee A, Haddad Zahmatkesh M, Mohammadhosseini N, Khalafy J, Emami S, Moshafi MH, Sorkhi M, Foroumadi A. Synthesis and in-vitro antibacterial activity of N-piperazinyl quinolone derivatives with 5-chloro-2-thienyl group. Daru. 2008;16:189–195. [Google Scholar]
  • 11.Letafat BS, Emami S, Mohammadhosseini N, Faramarzi MA, Samadi N, Shafiee A, Foroumadi A. Synthesis and antibacterial activity of new N-[2-(thiophen-3-yl)ethyl]piperazinyl quinolones. Chem. Pharm. Bull. 2007;55:894–898. doi: 10.1248/cpb.55.894. [DOI] [PubMed] [Google Scholar]
  • 12.Foroumadi A, Mohammadhosseini N, Emami S, Letafat B, Faramarzi MA, Samadi N, Shafiee A. Synthesis and antibacterial activity of new 7-piperazinyl-quinolones containing a functionalized 2-(furan-3-yl)ethyl. Arch. Pharm. Chem. Life Sci. 2007;340:47–52. doi: 10.1002/ardp.200600169. [DOI] [PubMed] [Google Scholar]
  • 13.Foroumadi A, Emami S, Mansouri S, Javidnia A, Saeid-Adeli N, Shirazi FH, Shafiee A. Synthesis and antibacterial activity of levofloxacin derivatives with certain bulky residues on piperazine rings. Eur. J. Med. Chem. 2007;42:985–992. doi: 10.1016/j.ejmech.2006.12.034. [DOI] [PubMed] [Google Scholar]
  • 14.Emami S, Foroumadi A, Faramarzi MA, Samadi N. Synthesis and antibacterial activity of quinolone-based compounds containing a coumarin moiety. Arch. Pharm. Chem. Life Sci. 2008;341:42–48. doi: 10.1002/ardp.200700090. [DOI] [PubMed] [Google Scholar]
  • 15.Shafiee A, Emami S, Ghodsi S, Najjari S, Sorkhi M, Samadi N, Faramarzi MA, Foroumadi A. Synthesis and antibacterial activity of N-[2-(2-naphthyl)ethyl] piperazinyl quinolones. J. Iranian Chem. Soc. 2009;6:325–333. [Google Scholar]
  • 16.Baron EJ, Finegold SM. Bailey Scott’s Diagnostic Microbiology. 11th ed. St. Louis: CV Mosby Company; 2002. pp. 235–236. [Google Scholar]
  • 17.Jazayeri S, Moshafi MH, Firoozpour L, Emami S, Rajabalian S, Haddad M, Pahlavanzadeh F, Esnaasharia M, Shafiee A, Foroumadi A. Synthesis and antibacterial activity of nitroaryl thiadiazole-gatifloxacin hybrids. Eur. J. Med. Chem. 2009;44:1205–1209. doi: 10.1016/j.ejmech.2008.09.012. [DOI] [PubMed] [Google Scholar]

Articles from Iranian Journal of Pharmaceutical Research : IJPR are provided here courtesy of Brieflands

RESOURCES