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Synthesis, characterization and biological activity studies on amide derivatives.

INTRODUCTION

Amides are multifunctional groups found in many molecules. Not only are they used as prodrugs (e.g. salicylamide), but also they possess diverse biological activities such as anticancer (Jung et al. 2009; Xu et al. 2010; Yurttas et al. 2014; Wang et al. 2014; Huczynski et al. 2015; Mathew et al. 2017), antimalarial (Delarue-Cochin et al. 2008; Kumar et al. 2011), insecticidal (Deng et al. 2016; Yang et al. 2016; Lv et al. 2018); antimicrobial (Huczynski et al. 2012; Soni and Soman 2014; Swapnaja et al. 2016; Wei et al. 2018), anti-inflammatory (Bai et al. 2018), antioxidant (Narender et al. 2011), antinociceptive (Czopek et al. 2016) and antithrombotic (Sashidhara et al. 2012), depending on their substituents. Moreover, amide carrying compounds were noted for their remarkable antibacterial (Mishra et al. 2008; Cui et al. 2017; Bi et al. 2018) and antifungal (Li et al. 2012; Sun et al. 2015; Yu et al. 2018) activities. It should be added that they have also attracted a great deal of attention for their significant anti-biofilm (Ballard et al. 2008; Richards et al. 2009; Rogers et al. 2010; Rane et al. 2012) and antiviral (Hao et al. 2012; Lan et al. 2017) activities.

As is known, the discovery of antibiotics made it possible to treat the infectious diseases that were once untreatable and enabled to save millions of lives by taking many dangerous bacterial infections under control. However, with the occurence of bacterial resistance and in regard to the increasing incidence of multidrug resistance in pathogenic bacteria, the identification of alternative antimicrobial drug targets to develop novel treatment strategies have become a necessity. Recently, it has been regarded that inactivating the quorum sensing (QS) system in bacteria by the use of QS inhibitors holds great promise for the treatment of infectious diseases. QS is a cell-to-cell communication system utilized by a wide variety of Gram (-) and Gram (+) bacteria to control the expression of virulence factors like elastase, extracellular protease, swarming, swimming motility and biofilm formation (de Kievit et al. 2000). Various types of screening have been carried out to find QS inhibitory molecules. Furanone derivatives, AHL analogs, synthetic compounds and some natural substances have been reported to possess QS inhibitory activity (Bosgelmez-Tinaz et al 2007; Galloway et al. 2011; Miandji et al. 2012).

Viruses have a simple structure and wholly depend on the host cells for almost all their vital functions. This situation makes it difficult to develop antiviral agents which are non-toxic for host cell metabolic systems. Antiviral agents that can be used against influenza A viruses (which pose great risks for human health), are also limited with NA inhibitors. These viruses belong to the Orthomixoviridae family and at times cause recurrent epidemics and pandemics within the global human population (Oxford 2000). Recurrent infections of influenza viruses in the human population are largely due to the continual changes occurring in the antigenic properties of virus surface glycoproteins (Laver 1984; Jimenez-Alberto et al. 2013). In particular, the changes of the viral surface antigens enable the virus to avoid the immunological defense of the host organism (Govorkova, 2000). Consequently, the control of influenza by vaccination is not completely effective. Therefore, a considerable effort is being made to develop new drugs and vaccines to combat influenza A viruses.

Hence, in this study, we synthesized a group of amide molecules with reference to p-aminophenylacetic acid and investigated their effects on biofilm formation and swarming motility in P. aeruginosa. Furthermore, the antiviral activities of these molecules were examined.

MATERIALS AND METHODS

Chemistry

All of the chemicals, reagents and solvents were purchased from Sigma Aldrich (St. Louis, MO, USA) and Merck (Darmstadt, Germany). Melting points were determined using Schmelzpunktbestimmer SMP II apparatus. For HPLC studies, an Agilent 1100 series system with a G1311A quaternary HPLC pump, a G1315A DAD detector, a G1379A vacuum degasser and a Kromasil 100 C18 5[micro]m, 250 x 4.6 mm column was used. The Rt (retention time) values were determined by an isocratic HPLC grade acetonitrile/water (60:40 v/v) mobile phase at a flow rate of 1 ml/min with DAD detector set at 254 nm. The IR spectra were recorded on a Schimadzu FTIR 8400 S Spectrometer. The NMR spectra were recorded (in DMSO-[d.sub.6]) with a Bruker spectrometer (Billerica, MA, USA) (300 MHz for [.sup.1]H-NMR and 75 MHz for [.sup.13]C-NMR, decoupled). The chemical shift values were expressed in ppm ([delta] scale) using tetramethylsilane as an internal standard. The mass spectral measurements were carried out by Electron Spray Ionization (ES) method on LC-MS-Agilent 1100. Elemental analysis was performed on Leco 215 CHNS-932 analyzer.

Synthesis of amide derivatives (1-6)

Firstly to obtain compound 1, p-aminophenylacetic acid (0.012 mol) was reacted with the equivalent moles of p-fluorobenzoylchloride in a chloroform media, while stirred at room temperature. Secondly, for compounds 2 and 3, the amide derivative (0.010 mol) was dissolved in concentrated sulphuric acid/methanol or ethanol media and refluxed. The precipitate was obtained through the neutralization reaction with sodium bicarbonate. Thirdly, to obtain compound 4 the methyl ester derivative was refluxed with hydrazine hydrate in an ethanol media. Fourthly, compound 5 was obtained through the reaction of hydrazide with ethyl isothiocyanate in an ethanol media. Finally, the thiosemicarbazide was reacted with concentrated sulphuric acid while stirring at room temperature for 45 minutes to obtain the compound 6 (Kucukguzel et al. 2006; Karakus et al. 2010). All of the compounds were purified with hot ethanol.

{4-[(4-Fluorobenzoyl)amino]phenyl}acetic acid (1): Cream solid. Yield 75%; m.p. 152 [degrees]C; MW: 273.2591 g/mol; Rt value: 7.69 min. FT-IR [u.sub.max]. ([cm.sup.-1]): 3323 (O-H and N-H), 1726 (amide C=O), 1645 (carboxylic acid C=O), 1223 (Ar-F). (CAS Number: 907947-59-5).

Methyl {4-[(4-fluorobenzoyl)amino]phenyl}acetate (2): Cream solid. Yield 79%; m.p. 148 [degrees]C; MW: 287.2857 g/mol; Rt value: 6.00 min. FT-IR [u.sub.max]. ([cm.sup.-1]): 3329 (N-H), 1742 (ester C=O), 1651 (amide C=O), 1221 (Ar-F). [.sup.1]H-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 3.62 ([.sup.3]H, s, -C[H.sub.3]), 3.65 (2H, s, -C[H.sub.2]-), 7.26 (2H, d, J: 8.40 Hz, Ar-H), 7.37 (2H, t, Ar-H), 7.68 (2H, d, J: 8.40 Hz, Ar-H), 8.04 (2H, t, Ar-H), 10.27 (1H, s, -CONH-). [.sup.13]C-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 39.57, 51.62, 115.12, 115.41, 120.39, 129.48, 129.60, 130.27, 130.39, 131.29, 131.33, 137.79, 162.37, 164.31 (amide C=O), 165.67, 171.67 (C=O). MS (ES m/z): 310 (M++Na), 180, 179, 101. Elemental analysis for [C.sub.16][H.sub.14] FN[O.sub.3] Calculated/Found (%): C: 66.89/66.28, H: 4.91/4.89, N: 4.88/4.72. (CAS Number: 2204929-37-1).

Ethyl {4-[(4-fluorobenzoyl)amino]phenyl}acetate (3): White solid. Yield 65%; m.p. 154-155 [degrees]C; MW: 301.3122 g/mol; FT-IR [u.sub.max]. ([cm.sup.-1]): 3337, 3298 (N-H), 1722 (ester C=O), 1647 (amide C=O), 1229 (Ar-F). [.sup.1]H-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 1.19 ([.sup.3]H, t, -C[H.sub.2]-C[H.sub.3]), 3.63 (2H, s, -C[H.sub.2]-), 4.05-4.12 (2H, q, - C[H.sub.2]-C[H.sub.3]), 7.26 (2H, d, J: 8.40 Hz, Ar-H), 7.34-7.40 (2H, m, Ar-H), 7.69 (2H, d, J: 8.40 Hz, Ar-H), 8.01-8.06 (2H, m, Ar-H), 10.26 (1H, s, -CONH-). [.sup.13]C-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 14.53, 40.26, 60.73, 115.65, 115.94, 120.89, 129.97, 130.23, 130.76, 130.88, 131.74, 131.78, 138.19, 162.87, 164.88 (amide C=O), 166.17, 171.75 (C=O). Elemental analysis for [C.sub.17][H.sub.16]FN[O.sub.3] Calculated/Found (%): C: 67.76/68.05, H: 5.35/5.50, N: 4.65/4.53. (CAS Number: 2204959-86-2).

4-Fluoro-N-[4-(2-hydrazinyl-2-oxoethyl)phenyl]benza-mide (4): White solid. Yield 86%; m.p. 352 [degrees]C (decomposed); MW: 287.2890 g/mol; Rt value: 2.70 min. FT-IR [u.sub.max] ([cm.sup.-1]): 3352, 3295, 3210 (N-H), 1645 (C=O), 1233 (Ar-F). [.sup.1]H-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 3.22 (2H, s, -C[H.sub.2]-), 4.22 (2H, b.s, -NH-N[H.sub.2]), 7.25 (2H, d, J: 8.70 Hz, Ar-H), 7.36 (2H, t, Ar-H), 7.65 (2H, d, J: 8.40 Hz, Ar-H), 8.02 (2H, t, Ar-H), 9.21 ([.sup.1]H, b.s, -NH-N[H.sub.2]), 10.23 (1H, s, -CONH-). [.sup.13]C-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 39.87, 115.11, 115.40, 120.34, 129.04, 130.24, 130.36, 131.28, 131.32, 131.59, 137.17, 162.35, 164.26 (amide C=O), 165.65, 169.66 (C=O). MS (ES m/z): 310 ( [M.sup.+]+Na), 180, 179, 101. Elemental analysis for [C15][H.sub.14]F[N.sub.3][O.sub.2] Calculated/Found (%): C: 62.71/63.37, H: 4.91/4.97, N: 14.63/14.21. (CAS Number: 2214835-31-9).

N-(4-{2-[2-(ethylcarbamothioyl)hydrazinyl]-2-oxoethyl} phenyl)-4-fluorobenzamide (5): White solid. Yield 79%; m.p. 226 [degrees]C; MW: 374.4325 g/mol; Rt value: 3.63 min. FT-IR [u.sub.max] ([cm.sup.-1]): 3314, 3196 (N-H), 1674, 1645 (C=O), 1219 (C=S), 1159 (Ar-F). [.sup.1]H-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 1.07 ([.sup.3]H, t, -C[H.sub.2]-C[H.sub.3]), 3.45 (4H, s, -C[H.sub.2]-C[H.sub.3] and -C[H.sub.2]-), 7.28 (2H, d, J: 8.70 Hz, Ar-H), 7.37 (2H, t, Ar-H), 7.67 (2H, d, J: 8.40 Hz, Ar-H); 7.93 (1H, t, [N.sub.4]H), 8.01-8.06 (2H, m, Ar-H), 9.17 (1H, b.s, N2H), 9.91 (1H, b.s, [N.sub.1]H), 10.24 (1H, s, -CONH-). [.sup.13]C-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 14.44, 37.13, 115.13, 115.42, 120.27, 129.40, 130.26, 130.38, 130.79, 131.27, 131.31, 137.49, 162.36, 164.27 (amide C=O), 165.66, 169.95 (C=O), 181.25 (C=S). Elemental analysis for [C.sub.18][H.sub.19]F[N.sub.4][O.sub.2]S Calculated/Found (%): C: 57.74/58.31, H: 5.11/5.27, N: 14.96/14.94, S: 8.56/7.90.

N-(4-{[5-(ethylamino)-1,3,4-thiadiazol-2-yl]methyl} phenyl)-4-fluorobenzamide (6): Light brown solid. Yield 40%; m.p. 310-311 [degrees]C; MW: 365.4248 g/mol; Rt value: 4.20 min. FT-IR [u.sub.max] ([cm.sup.-1]): 3310, 3188 (OH and N-H), 1651 (C=O), 1231 (Ar-F), 760 (C-S-C). [.sup.1]H-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 1.13 ([.sup.3]H, t, -C[H.sub.2]-C[H.sub.3]), 3.18-3.27 (2H, m, -C[H.sub.2]-C[H.sub.3]), 4.13 (2H, s, -C[H.sub.2]-), 7.27 (2H, d J: 8.70 Hz, Ar-H), 7.37 (2H, t, Ar-H), 7.57 ([.sup.1]H, t, -NH-), 7.70 (2H, d, J: 8.40 Hz, Ar-H), 8.03 (2H, t, Ar-H), 10.27 (1H, s, -CONH-). [.sup.13]C-NMR (DMSO-[d.sub.6]/TMS) d (ppm): 14.24, 34.99, 115.13, 115.42, 120.61, 128.82, 130.27, 130.39, 131.27, 131.30, 133.24, 137.82, 157.09, 162.37, 164.32, 165.67, 168.78 (amide C=O), 169.69. MS (ES m/z): 357 ([M.sup.+]+1), 189, 182, 179, 101. Elemental analysis for [C.sub.18][H.sub.17]F[N.sub.4]OS.1/2[H.sub.2]O Calculated/Found (%): C: 59.16/59.34, H: 4.96/4.87, N: 15.33/15.18, S: 8.77/8.74.

Anti-biofilm activity

The anti-biofilm capacities of the substituted-amide derivatives were examined using the biofilm assay. The overnight culture of P. aeruginosa PA01 strain was diluted to an O[D.sub.600] of 0.02. 1mL aliquots of the diluted cultures were allocated in polystyrene tubes and incubated at 32[degrees]C for 10 h. Nonadherent cells were removed. The biofilms were dyed with 1 ml of crystal violet (0.3%) and the absorbance was measured at 570 nm using a spectrophotometer (Truchado et al. 2009).

Swarming motility assay

The swarming motility was measured as described by Rashid et al. (2000). Five microliters of PA01 cultures were inoculated onto the surface of swarm plates containing Bacto Agar (0.5%), Nutrient Broth and glucose (1%). This was completed both in the presence and absence of the test compounds and then incubated overnight at 37[degrees]C for 24 h.

Cells and viruses

Madin-Darby canine kidney (MDCK) cells were used for plaque inhibition assays. The cells were grown in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal calf serum (Gibco), penicillin G (100 U/mL) and streptomycin (100 [micro]g/mL), and maintained in a humidified atmosphere containing 5% C[O.sub.2] at 37 [degrees]C. The antiviral activities of the synthesized compounds were investigated on influenza A virus, strain A/WSN/33 (H1N1). The viruses were grown in the allantoic cavity of 10 day-old chick embryos at 35.5 [degrees]C for 48 h. The allantoic fluid was clarified by centrifugation at 3,000g for 10 minutes, passed through 0.45 [micro]m sterile filter, and the filtrate was stored in small aliquots at 80 [degrees]C

Plaque inhibition assay

For the plaque inhibition assay, confluent monolayer cultures of MDCK cells in 12-well plate were washed twice with DMEM (-), and infected with influenza viruses at the appropriate multiplicity of infection (moi). After adsorption for 30 min at 37 [degrees]C, virus inoculums were completely removed, and the cell monolayers were overlaid with a maintenance medium (DMEM containing 0.6% agarose, 0.2% Bovine Serum Albumin and 4 mg/mL TPCK-treated trypsin). In test conditions, synthesized compounds were added to a maintenance medium at defined concentrations. The plates were incubated at 34 [degrees]C for 2-3 days, and plaques were visualized by staining the cells with amido black (Turan et al. 1996; Guveli et al 2018).

RESULT AND DISCUSSION

In the present study, six amide derivatives (compounds 1-6) were synthesized from p-aminophenylacetic acid. The synthetic route of compounds is represented in Scheme 1.

Their purity was proven by TLC, HPLC and elemental analyses. Also, their structures were elucidated by FT-IR, [.sup.1]H-NMR, [.sup.13]C-NMR and MS spectral methods. IR absorption bands due to amide C=O and aromatic C-F stretching bands were recorded at 1726-1645 and 1233- 1159 [cm.sup.-1], respectively. According to the [.sup.1]H-NMR spectra, the -C[H.sub.2]- and amide N-H peaks were observed at 3.22-4.13 and 10.23-10.27 ppm as singlets, in turn. In addition, the [.sup.13]C-NMR spectra exhibited resonances at 164.26-168.78 assigned for amide C=O. Aside from these, the elemental analysis and MS spectral data results were in accordance with the compounds structures.

The synthesized compounds' anti-biofilm capacities were confirmed by the biofilm assay Biofilm formation causes serious problems in both medicine and industry Biofilm-associated bacteria are more resistant to antimicrobials than planktonic cells. We tested the effects of compounds 1-6 on biofilm formation of P. aeruginosa PA01. According to the results these molecules inhibited biofilm formation by 8.7-25.6% at 200 [micro]M concentration. Among the tested compounds, compound 3 was found to be the most active one, reducing the biofilm formation by 25.6% in P. aeruginosa PA01 at a concentration of 200 [micro]M. We also performed a swarming motility assay. Swarming motility plays an important role in the early stages of biofilm development and antibiotic resistance. The swarming motility of P. aeruginosa PAO1 was assayed both in the presence and absence of test compounds. Swarming plates were supplemented with 200 [micro]M synthesized compounds. The treatment of P. aeruginosa PAO1 with these compounds resulted in reductions in swarming motility by 18.3-33.8% (Table 1, Figure 1).

The antiviral activity of compounds 1-6 were revealed by using plaque inhibition assays on influenza A viruses. Among the synthesized compounds tested on influenza virus plaque formation, Compound 6 showed an inhibitory effect (Figure 2). Plaque formation by influenza A viruses was almost completely inhibited by this compound at concentrations of 10 [micro]g/mL. Compound 6 did not show any cytopathic effect on MDCK cells at 5-20 [micro]g/mL (Figure 2).

Influenza viruses are enveloped viruses having a negative polarity and a segmented RNA genome. Despite the simple structure, they have multi-stage complex replication strategies. Therefore, it is difficult to reach a firm conclusion about the action mechanism of compound 6 on the influenza virus replication based on the results of the plaque inhibition assay. The research will continue to elucidate the mode of action of this molecule. Compound 6 differs from the other 5 compounds in terms of thiadiazole group. This group may therefore be considered as important for antiviral activity (Gan et al. 2017).

CONCLUSION

A series of amide derivatives (1-6) were obtained from p-aminophenyl acetic acid, characterized by several spectroscopic methods (IR, NMR, MS) and elemental analysis. They were also evaluated for their anti-biofilm and antiviral effects. The results suggested that compounds 1-6 could be used as antibiofilm agents in combination with conventional antibiotics to increase the efficiency of current antimicrobials. Also, depending on antiviral activity studies, it can be said that compound 6 has potential as an anti-influenza virus agent. Further studies are in progress.

Peer-review: Externally peer-reviewed.

Author Contributions: Concept--ST., S.K.; Design--ST., K.T., S.U., S.K., G.B.T.; Supervision--K.T., S.K., G.B.T.; Resource--ST., K.T., S.U., S.K., G.B.T.; Materials--ST., K.T., S.U., S.K., G.B.T.; Data Collection and/or Processing--ST., K.T., S.U., S.K., G.B.T.; Analysis and/or Interpretation--ST., K.T., S.U., S.K., G.B.T.; Literature Search--ST., K.T., S.K., G.B.T.; Writing--ST., K.T., S.K., G.B.T.; Critical Reviews--K.T., S.K., G.B.T.

Conflict of Interest: The authors have no conflict of interest to declare.

Financial Disclosure: This study was financially supported by the Marmara University Scientific Research Committee (Project No: SAG-C-DRP-070617-0343).

REFERENCES

* Bai R, Sun J, Liang Z, Yoon Y, Salgado E, Feng A, Oum Y, Xie Y, Shim H (2018) Anti-inflammatory hybrids of secondary amines and amide-sulfamide derivatives. Eur J Med Chem 150: 195-205. [CrossRef]

* Ballard TE, Richards JJ, Wolfe AL, Melander C (2008) Synthesis and antibiofilm activity of a second-generation reverse-amide oroidin library: a structure-activity relationship study. Chem Eur J 14: 10745-10761. [CrossRef]

* Bi F, Ji S, Venter H, Liu J, Semple SJ, Ma S (2018) Substitution of terminal amide with [.sup.1]H-1,2,3-triazole: identificaiton of unexpected class of potent antibacterial agents. Bioorg Med Chem Lett 28: 884-891. [CrossRef]

* Bosgelmez-Tinaz G, Ulusoy S, Ugur A, Ceylan O (2007) Inhibition of QS-regulated behaviors by Scorzonera sandrasica. Curr Microbiol 55:114-118. [CrossRef]

* Cui YJ, Rao XP, Shang SB, Song ZQ, Shen MG, Liu H (2017) Synthesis, structure analysis and antibacterial activity of N-[5-dehy-droabietyl-[1,3,4]thiadiazol-2-yl]-aromatic amide derivatives. J Saudi Chem Soc 21: 258-263. [CrossRef]

* Czopek A, Salat K, Byrtus H, Rychtyk J, Pawlowski M, Siwek A, Soluch J, Mureddu V, Filipek B (2016) Antinociceptive activity of novel amide derivatives of imidazolidine-2,4-dione in a Mouse model of acute pain. Pharmacol Rep 68: 529-535. [CrossRef]

* De Kievit TR, Iglewski BH (2000) Bacterial quorum sensing in pathogenic relationships. Infect Immun 68: 4839-4849. [CrossRef]

* Delarue-Cochin S, Grellier P, Maes L, Mouray E, Sergheraert C, Melnyk P (2008) Synthesis and antimalarial activity of carbamate and amide derivatives of 4-anilinoquinoline. Eur J Med Chem 43: 2045-2055. [CrossRef]

* Deng XL, Zhang L, Hu XP, Yin B, Liang P Yang XL (2016) Target-based design, synthesis and biological activity of new pyrazole amide derivatives. Chinese Chem Lett 27: 251-255. [CrossRef]

* Galloway WRJD, Hodgkinson JT, Bowden SD, Welch M, Spring DR (2011) Quorum sensing in gram-negative bacteria: Small molecule modulation of AHL and AI-2 quorum sensing pathways. Chem Rev 111 :28-67. [CrossRef]

* Gan X, Hu D, Chen Z, Wang Y, Song B (2017) Synthesis and antiviral evaluation of novel 1,3,4-oxadiazole/thiadiazole chalcone conjugates. Bioorg Med Chem Lett 27: 4298-4301. [CrossRef]

* Govorkova EA, Gambaryan AS, Claas EC, Smirnov YA (2000) Amino acid changes in the hemagglutinin and matrix proteins of influenza a (H2) viruses adapted to mice. Acta Virol 44: 241-248.

* Guveli S, Turan K, Ulkuseven B (2018) Nickel (II)-PPh3 complexes with ONS and ONN chelating thiosemicarbazones: synthesis and inhibition potential on influenza A viruses, Turk J Chem 42(2): 371-384. [CrossRef]

* Hao LH, Li YP, He WY, Wang HQ, Shan GZ, Jiang JD, Li YH, Li ZR (2012) Synthesis and antiviral activity of substituted bisaryl amide compounds as novel influenza virus inhibitors. Eur J Med Chem 55: 117-124. [CrossRef]

* Huczyhski A, Janczak J, Stefahska J, Antoszczak M, Brzezinski B (2012) Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic-salinomycin. Bioorg Med Chem Lett 22: 4697-4702. [CrossRef]

* Huczyhski A, Klejborowska G, Antoszczak M, Maj E, Wietrzyk J (2015) Anti-proliferative activity of monensin and its tertiary amide derivatives. Bioorg Med Chem Lett 25: 4539-4543. [CrossRef]

* Jimenez-Alberto A, Alvarado-Facundo E, Ribas-Aparicio RM, Castelan-Vega JA (2013) Analysis of adaptation mutants in the hemagglutinin of the influenza A(H1N1) pdm09 virus. PLoS One 8: 70005. [CrossRef]

* Jung M, Park N, Moon HI, Lee Y, Chung WY, Park KK (2009) Synthesis and anticancer activity of novel amide derivatives of non-acetal deoxoartemisinin. Bioorg Med Chem Lett 19: 6303-6306. [CrossRef]

* Karakus S, Coruh U, Barlas-Durgun B, Vazquez-Lopez EM, Ozbas-Turan S, Akbuga J, Rollas S (2010) Synthesis and cytotoxic activity of some 1,2,4-triazoline-3-thione and 2,5-disubstituted-1,3,4-thiadiazole derivatives. Marmara Pharm J 14: 84-90. [CrossRef]

* Kumar N, Khan SI, Atheaya H, Mamgain R, Rawat DS (2011) Synthesis and in vitro antimalarial activity of tetraoxane-amine/amide conjugates. Eur J Med Chem 46: 2816-2827. [CrossRef]

* Kucukguzel G, Kocatepe A, De Clercq E, Sahin F, Gulluce M (2006) Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide. Eur J Med Chem 41: 353-359. [CrossRef]

* Lan X, Xie D, Yin L, Wang Z, Chen J, Zhang A, Song B, Hu D (2017) Novel [alpha],[beta]-unsaturated amide derivatives bearing [alpha]-amino phosphonate moiety as potential antiviral agents. Bioorg Med Chem Lett 27: 4270-7273. [CrossRef]

* Laver WG (1984) Antigenic variation and the structure of influenza virus glycoproteins. Microbiol Sci 1: 37-43.

* Li S, Cui C, Wang MY, Yu SJ, Shi YX, Zhang X, Li ZM, Zhao WG, Li BJ (2012) Synthesis and fungicidal activity of new fluorine-containing mandelic acid amide compounds J Fluor Chem 137: 108-112. [CrossRef]

* Lv M, Liu G, Jia M, Xu H (2018) Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole scaffold as insecticidal/acaricidal agents. Bioorg Chem 81: 88-92. [CrossRef]

* Mathew B, Hobrath JV, Connelly MC, Guy RK, Reynolds RC (2017) Diverse amide analogs of sulindac for cancer treatment and prevention. Bioorg Med Chem Lett 27: 4614-4621. [CrossRef]

* Miandji MA, Ulusoy S, Dundar Y, Ozgen S, Kaynak Onurdag F, Bosgelmez-Tinaz G, Noyanalpan N (2012) Synthesis and biological activities of some 1,3-benzoxazol-2([.sup.3]H)-one derivatives as anti-quorum sensing agents. ARZNEIMITTELFORSCH 62(7): 330-334. [CrossRef]

* Mishra A, Kaushik NK, Verma AK, Gupta R (2008) Synthesis, characterization and antibacterial activity of cobalt (III) complexes with pyridine-amide ligands. Eur J Med Chem 43: 2189-2196. [CrossRef]

* Narender T, Rajendar K, Sarkar S, Singh VK, Chaturvedi U, Khanna AK, Bhatia G (2011) Synthesis of novel N-(2-oxo-2-p-tolylethyl)amide derivatives and their antidyslipidemic and antioxidant activity. Bioorg Med Chem Lett 21: 6393-6397. [CrossRef]

* Oxford JS (2000) Influenza A pandemics of the 20th century with special reference to 1918: virology, pathology and epidemiology. Rev Med Virol 10:119-133. [CrossRef]

* Rane RA, Sahu NU, Shah CP (2012) Synthesis and antibiofilm activity of marine natural product-based 4-thiazolidinones derivatives. Bioorg Med Chem Lett 22: 7131-7134. [CrossRef]

* Rashid MH, Kornberg A (2000) Inorganic polyphosphate is needed for swimming, swarming and twitching motilities of P. aeruginosa. P Natl Acad Sci USA 97: 4885-4890. [CrossRef]

* Richards JJ, Reyes S, Stowe SD, Tucker AT, Ballard TE, Mathies LD, Cavanagh J, Melander C (2009) Amide isosteres of oroidin: assessment of antibiofilm activity and c. elegans toxicity. J Med Chem 52: 4582-4585. [CrossRef]

* Rogers SA, Bero JD, Melander C (2010) Chemical synthesis and biological screening of 2-aminoimidazole-based bacterial and fungal antibiofilm agents. ChemBioChem 11: 396-410. [CrossRef]

* Sashidhara KV, Palnati GR, Avula SR, Singh S, Jain M, Dikshit M (2012) Synthesis and evaluation of anti-thrombotic activity of benzocoumarin amide derivatives. Bioorg Med Chem Lett 22: 3115-3121. [CrossRef]

* Soni JN, Soman SS (2014) Synthesis and antimicrobial evaluation of amide derivatives of benzodifuran-2-carboxylic acid. Eur J Med Chem 75: 77-81. [CrossRef]

* Sun M, Yang HH, Tian L, Li JQ, Zhao WG (2015) Design, synthesis, and fungicidal activities of imino diacid anologs of valine amide fungicides. Bioorg Med Chem Lett 25: 5729-5731. [CrossRef]

* Swapnaja KJM, Yennam S, Chavalli M, Poornachandra Y, Kumar CG, Muthusamy K, Jayaraman VB, Arumugam P, Balasubramanian S, Sriram KK (2016) Design, synthesis and biological evaluation of diaziridinyl quinone isoxazole hybrids. Eur J Med Chem 117: 85-98. [CrossRef]

* Truchado P, Gil-Izquierdo A, Tomas-Barberan F, Allende A (2009) Inhibition by chestnut honey of n-acyl-l-homoserine lactones and biofilm formation in erwinia carotovora, yersinia enterocolitica, and aeromonas hydrophila. J Agr Food Chem 57: 11186-11193. [CrossRef]

* Turan K, Nagata K, Kuru A (1996) Antiviral effect of Sanicula europaea L leaves extract on influenza virus-infected cells. Biochem Biophys Res Commun 225: 22-26. [CrossRef]

* Wang YH, Goto M, Wang LT, Hsieh KY, Morris-Natschke SL, Tang GH, Long CL, Lee KH (2014) Multidrug resistance-selective anti-proliferative activity of piperamide alkaloids and synthetic analogues. Bioorg Med Chem Lett 24: 4818-4821. [CrossRef]

* Wei Q, Wang X, Cheng JH, Zeng G, Sun DW (2018) Synthesis and antimicrobial activities of novel sorbic and benzoic acid amide derivatives. Food Chem 268: 220-232. [CrossRef]

* Xu Y, Guo ZJ, Wu N (2010) Two new amide alkaloids with anti-leukemia activities from aconitum taipeicum. FTRPAE 81: 1091-1093.

* Yang ZB, Hu DY, Zeng S, Song BA (2016) Novel hydrazone derivatives containing pyridine amide moiety: design, synthesis, and insecticidal activity. Bioorg Med Chem Lett 26: 1161-1164. [CrossRef]

* Yu X, Teng P, Zhang YL, Xu ZJ, Zhang MZ, Zhang WH (2018) Design, synthesis andd antifungal activity evaluation of coumarin-3-carboxamide derivatives. FTRPAE 127: 387-395.

* Yurttas L, Demirayak S, Ilgin S, Atli O (2014) In vitro antitumor activity evaluation of some 1,2,4-triazine derivatives bearing piperazine amide moiety against breast cancer cells. Bioorg Med Chem 22: 6313-6323. [CrossRef]

Sevda Turk (1)[iD], Kadir Turan (2)[iD], Seyhan Ulusoy (3)[iD], Sevgi Karakus (1*)[iD], Gulgun Bosgelmez-Tinaz (2)[iD]

(1) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, 34668, Istanbul, Turkey

(2) Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Marmara University, 34668, Istanbul, Turkey

(3) Department of Biology, Faculty of Arts and Sciences, Suleyman Demirel University, 32260, Isparta,Turkey

Cite this article as: Turk S, Turan K, Ulusoy S, Karakus S, Bosgelmez-Tinaz G. (2018) Synthesis, Characterization and biological activity studies on amide derivatives. Istanbul J Pharm 48 (3): 76-81.

This study was presented at the "V. International Multidisciplinary Congress of Eurasia (IMCOFE'18)", "24-26 July 2018, "Barcelona-Spain".

Address for Correspondence :

Sevgi Karakus, e-mail: skarakus@marmara.edu.tr

Received: 12.09.2018

Accepted: 25.10.2018

DOI: 10.26650/IstanbulJPharm.2018.18007
Table 1. Effect of compound 1-6 derivatives on the biofilm formation
and swarming motility of P. aeruginosa PA01 strain. The data represents
the averages from the results of three independent experiments.

Biofilm Formation  Swarming Motility
Inhibition (%)     Inhibition (%)

1  13.9            28.9
2   8.7            22.4
3  25.6            18.3
4  13.0            31.4
5  19.0            32.2
6  17.3            33.8
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Title Annotation:Original Article
Author:Turk, Sevda; Turan, Kadir; Ulusoy, Seyhan; Karakus, Sevgi; Bosgelmez-Tinaz, Gulgun
Publication:Journal of the Faculty of Pharmacy of Istanbul University
Date:Dec 1, 2018
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