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Synthesis and antimicrobial activity of derivatives of 1H-benzo[de]isoquinoline-1,3(2H)-dione

  • Bożena Kuran EMAIL logo , Mariola Krawiecka , Jerzy Kossakowski , Ksenia Szymanek , Marta Kierzkowska and Grażyna Młynarczyk
Published/Copyright: November 12, 2012
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 18 Issue 5-6

Abstract

Five aminoalkyl 1H-benzo[de]isoquinoline-1,3(2H)-diones were synthesized and evaluated for antimicrobial activity. Microorganisms used in this study included aerobic and facultative anaerobic bacteria Staphylococcus aureus, Escherichia coli and Stenotrophomonas maltophilia, and obligatory anaerobes Bacteroides fragilis, Bacteroides thetaiotaomicron and Propionibacterium acnes. Moreover, Candida albicans yeast was used. The minimum inhibitory concentration (MIC) was determined for the test compounds. Among the tested derivatives, two compounds 1 and 2 have shown the most potent antibacterial as well as antifungal activities.

Keywords: antifungal activity; antimicrobial activity; 1H-benzo[de]isoquinoline-1,3(2H)-dione

Introduction

It is known that antibiotic therapy, despite the unquestioned benefits of eliminating the pathogenic microorganisms, causes disorder in the composition of normal microflora and, in particular, the composition of anaerobes. This leads to various disorders, most often post-treatment diarrheas. It is also known that the sensitivity of strictly anaerobic bacteria to antimicrobial agents considerably differs from that of the relative anaerobes and aerobes. There are antibiotics that do not work for absolute anaerobes (aminoglycosides, cephalosporins) (Marshall and Blair, 1999; Zejc and Gorczyca, 1999; Durante-Mangoni et al., 2009) and those that affect only the absolute anaerobes (metronidazole) (Ralph and Kirby, 1975; Gulaid et al., 1978; Tall et al., 1978). In some infections (e.g., periodontitis), it is appropriate to administer an antibiotic acting only on anaerobes, because it does not interfere with the aerobic flora, which can have a very strong influence on the patient’s condition and health. The second problem is resistance to antibiotics, which generates a greater need for alternative treatments. Therefore, searching for selective microbial agents still seems important from the clinical point of view. Heterocyclic compounds such as succinimide, maleimides, glutarimides and their derivatives, other than anticancer and anticonvulsant agents (Sami et al., 2000; Braña et al., 2001, 2004; Bailly et al., 2003; Muth et al., 2003; Takada et al., 2004; Kazantsev et al., 2005; Hariprakasha et al., 2007; Quaquebeke et al., 2007; Schmitz et al., 2007; Sissi et al., 2007; Huang et al., 2009; Tian et al., 2009; Wu et al., 2009; Young et al., 2010; Mukherjee et al., 2011), may also exhibit antibacterial and antifungal properties (Haeberle and Eberle, 1982; Itoh et al., 1983; Takatori et al., 1985; Iragashi et al., 1990; Cechine Filho et al., 1994; Pereira et al., 1995; Zentz et al., 2002a,b, 2004).

On the basis of the information above and the results of our previous work on 17-azapentacyclo[6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaen-16,18-dione (Kuran et al., 2010, 2012), we synthesized five derivatives of 1H-benzo[de]isoquinoline-1,3(2H)-dione (1–5, Equation 1) and evaluated their microbial activity. Four of these derivatives (1–3, 5) have been obtained previously (Mattocks and Hutchison, 1948; Gray et al., 1955; Zee-Cheng and Cheng, 1985) by using different methodology.

Results and discussion

All compounds 1–5 were tested against aerobic bacteria Staphylococcus aureus, Stenotrophomonas maltophilia, Escherichia coli as well as selected obligatory anaerobes Propionibacterium acnes, Bacteroides fragilis and Bacteroides thetaiotaomicron and yeast strain Candida albicans.

These compounds show much better activity against the selected strains of aerobic bacteria then derivatives of 17-azapentacyclo [6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaen-16,18-dione studied by us previously (Kuran et al., 2010, 2012). The best activity is observed for compound 1, which inhibits the growth of all bacterial strains. Such activity has not been observed in any case for derivatives of 17-azapentacyclo [6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaen-16,18-dione. The activity results are shown in Table 1.

Table 1

MIC values (mg/L) of compounds 1–5 determined for different microorganisms.

StrainCompound
12345
S. aureus ATCC 25923512>512>512>512>512
S. maltophilia CO 2275512>512>512>512>512
E. coli ATCC 25922512>512>512>512>512
P. acnes ATCC 691964128>512n.d.n.d.
B. thetaiotaomicron ATCC 29741512>512>512n.d.n.d.
B. fragilis ATCC 252856464>512n.d.n.d.
C. albicans ATCC 14053128512512>512512
[1]

Derivatives of 1H-benzo[de]isoquinoline-1,3(2H)-dione show much better activity against the anaerobic bacteria. Compound 1 inhibits the growth of all selected anaerobic bacterial strains at a concentration of 512 mg/L. In addition, it exhibits activity against P. acnes and B. fragilis (both obligatory anaerobes) at a concentration of 64 mg/L. Similarly interesting results were obtained for compound 2. It inhibits the growth of bacteria P. acnes at a concentration of 128 mg/L, and also B. fragilis at a concentration of 64 mg/L.

In light of the results of our previous and current studies, it can be suggested that the antimicrobial activity of the tested imide derivatives depends on two factors, namely, the imide structure and the nature of the aminoalkyl substituent. However, we are unable to say which of these elements has a greater impact on activity. The two classes of the considered imides, 1H-benzo[de]isoquinoline-1,3(2H)-dione and 17-azapentacyclo[6.6.5.02,7.09,14.015,19] nonadeca-2,4,6,9,11,13-hexaen-16,18-dione, have a fairly large volume but are arranged differently in space (Figure 1).

Figure 1 Design strategy of spatial imide arrangement. Derivatives of 17-azapentacyclo[6.6.5.02,7.09,14.015,19] nonadeca-2,4,6,9,11,13- hexaen-16,18-dione (left) and 1H-benzo[de]isoquinoline-1,3(2H)-dione (right) are shown.
Figure 1

Design strategy of spatial imide arrangement. Derivatives of 17-azapentacyclo[6.6.5.02,7.09,14.015,19] nonadeca-2,4,6,9,11,13- hexaen-16,18-dione (left) and 1H-benzo[de]isoquinoline-1,3(2H)-dione (right) are shown.

Conclusions

Compounds 1 and 2 are easy to synthesize and possess significant antimicrobial activity.

Experimental

Melting points were determined in open capillaries using Electrothermal 9100 apparatus and are uncorrected. NMR spectra were recorded in DMSO-d6 on a Bruker VMNRS300 instrument operating at 300 MHz (1H NMR) and 75 MHz (13C NMR). Mass spectral ESI (electrospray ionization) measurements were carried out on a Mariner Perspective-Biosystem instrument with TOF detector. The spectra were obtained in the positive ion mode with a declustering potential of 140–300 V. Silica gel column chromatography was conducted using Merck Kieselgel 0.05–0.2 mm (70–325 mesh ASTM) and eluting with chloroform or chloroform/methanol, 250:1. Reactions were monitored by thin layer chromatography (TLC) on silica gel (plates with 254 nm fluorescent indicator, layer thickness 0.2 mm, Kieselgel G., Merck), eluting with chloroform/methanol, 50:1.

General procedure for preparation of imides 1–5

A mixture of 1H-benzo[de]isoquinoline-1,3(2H)-dione (0.01 mol), powdered anhydrous K2CO3 (0.01 mol), a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and a chloroalkylamine hydrochloride (0.01 mol) in acetone (30 mL) was heated for 8–14 h, as determined by TLC analysis. After the reaction was completed, the inorganic material was filtered off and the filtrate was concentrated. The residue of 1–5 was purified by column chromatography. All products were converted to hydrochlorides and salts were crystallized from methanol.

2-[2-(Dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (1)

Obtained as C16H16N2O2‧HCl; M = 268.31‧HCl; yield 82%; mp 283–284°C (lit mp 283–284°C; Zee-Cheng and Cheng, 1985); 1H NMR: δ 9.64 (s, 1H, HCl), 8.54–8.49 (m, 4H, Ar-H), 7.93–7.88 (m, 2H, Ar-H), 4.37 (t, 2H, C2′-H, J = 5.8 Hz), 3.31 (m, 2H, C1′-H), 2.80 (s, 6H, -CH3); 13C NMR: δ 35.1, 42.6, 54.6, 122.2, 127.2, 127.6, 130.8, 131.3, 134.5, 163.9; MS: m/z 269.2 (100%) [M+H+].

2-[2-(Diethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (2)

Obtained as C18H20N2O2‧HCl; M = 296.36‧HCl; yield 86%; mp 267–268°C (lit mp 257–259°C; Gray et al., 1955); 1H NMR: δ 9.91 (s, 1H, HCl), 8.55–8.49 (m, 4H, Ar-H), 7.93–7.88 (m, 2H, Ar-H), 4.40 (t, 2H, C2′-H, J = 6.9 Hz), 3.36–3.28 (m, 4H, C1′-H, -CH2-), 1.26 (t, 6H, -CH3, J = 7.0 Hz); 13C NMR: δ 8.4, 34.2, 46.5, 47.3, 122.1, 127.2, 127.5, 130.8, 131.3, 134.5, 163.7; MS: m/z 297.2 (100%) [M+H+].

2-[2-(Morpholino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (3)

Obtained as C18H18N2O3‧HCl; M = 310.35‧HCl; yield 90%; mp 277–278°C (lit mp 244°C; Mattocks and Hutchison, 1948); 1H NMR: δ 10.77 (s, 1H, HCl), 8.53–8.47 (m, 4H, Ar-H), 7.92–7.86 (m, 2H, Ar-H), 4.46–4.33 (m, 2H, C2′-H), 4.01–3.94 (m, 2H, H-morpholine), 3.78–3.62 (m, 4H, H-morpholine), 3.52–3.40 (m, 2H, H-morpholine), 3.20–3.15 (m, 2H, C1′-H); 13C NMR: δ 22.4, 34.5, 51.4, 63.2, 122.2, 127.3, 127.6, 130.8, 131.3, 134.5, 163.9; MS: m/z 311.2 (100%) [M+H+], 333.2 (28%) [M+Na+].

2-[2-(Piperidino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (4)

Obtained as C19H20N2O2‧HCl; M = 308.37‧HCl; yield 79%; mp 287–291°C; 1H NMR: δ 9.52 (s, 1H, HCl), 8.54–8.49 (m, 4H, Ar-H), 7.93–7.88 (m, 2H, Ar-H), 4.43–4.40 (m, 2H, C2′-H), 3.65–3.50 (m, 2H, C1′-H), 3.40 (m, 2H, H-piperidine), 3.20–2.80 (m, 2H, H-piperidine), 1.82–1.79 (m, 2H, H-piperidine), 1.69–1.55 (m, 3H, H-piperidine), 1.43–1.39 (m, 1H, H-piperidine); 13C NMR: δ 21.3, 22.3, 34.4, 52.4, 53.5, 122.2, 127.2, 127.5, 130.8, 131.3, 134.5, 163.9; MS: m/z 309.2 (100%) [M+H+].

2-[3-(Dimethylamino)propyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (5)

Obtained as C17H18N2O2‧HCl; M = 282.34‧HCl; yield 92%; mp 295–296°C (lit mp 295°C; Gray et al., 1955); 1H NMR (300 MHz, DMSO-d6): δ 9.63 (s, 1H, HCl), 8.53–8.47 (m, 4H, Ar-H), 7.92–7.87 (m, 2H, Ar-H), 4.13 (t, 2H, C3′-H, J = 6.7), 3.32–3.30 (m, 2H, C1′-H), 3.17–3.12 (m, 2H, C2′-H), 2.73 (s, 6H, -CH3); 13C NMR: δ 23.00, 36.93, 42.11, 54.51, 122.16, 127.23, 127.50, 130.73, 131.31, 134.38, 163.73; MS: m/z 283.2 (100%) [M+H+].

Microbiology

Organisms

Standard strains of S. aureus ATCC 25923, E. coli ATCC 25922, C. albicans ATCC 14053, P. acnes ATCC 6919, B. thetaiotaomicron ATCC 29741, B. fragilis ATCC 25285 and one clinical isolate S. maltophilia CO 2275 were used.

Screening for antimicrobial activity

Compounds were tested for bacteriostatic activity at a concentration of 512 mg/L, and if the growth was inhibited a double dilution of the compound was prepared. A method according to CLSI (Clinical and Laboratory Standards Institute, 2006) directives was applied.

The tested substances were dissolved in DMSO and then the solutions were added to brain heart infusion broth (BHI-B) medium to a final concentration of 512 mg/L.

The aerobic bacteria were cultured on plates with BHI agar (BHI-A) medium supplemented with 7% horse blood at temperature 35–37°C under aerobic atmosphere for 18–24 h. Anaerobes were cultured in Schaedler agar with 5% of sheep blood at 35–37°C for 48 h under anaerobic atmosphere. The fungal strain was cultured in the Sabouraud agar (SA), at the same temperature and atmosphere, but for at least 24 h. The cultures which were in mid-logarithmic phase of growth were suspended in 0.9% NaCl to obtain 0.5 Mac Farland’s optical density and in the case of anaerobes the value of 1.0 in the same scale. 1.0–9.0×105 cells (0.1 mL of the prepared suspension) were added to sample tubes with 2 mL of BHI-B broth medium containing the tested substances. For anaerobes all media were pre-reduced. Samples were incubated at temperature 35–37°C for 24–48 h and in the case of anaerobes for 48–60 h. If after 48 h (60 h for anaerobes), growth was absent, the substance was noted as potentially possessing antimicrobial activity.

In all experiments, strain vitality controls and a DMSO antimicrobial activity control were performed at the used concentrations.

Corresponding author: Bożena Kuran, Department of Medical Chemistry, Medical University of Warsaw, 3 Oczki Str., 02-007 Warsaw, Poland

References

Bailly, C.; Carrasco, C.; Joubert, A.; Bal, C.; Wattez, N.; Hildebrand, M. P.; Lansiaux, A.; Colson, P.; Houssier, C.; Cacho, M.; et al. Chromophore-modified bisnaphthalimides: DNA recognition, topoisomerase inhibition, and cytotoxic properties of two mono- and bisfuronaphthalimides. Biochemistry 2003, 42, 4136–4150.Search in Google Scholar

Braña, M. F.; Cacho, M.; Gradillas, A.; de Pascual-Teresa, B.; Ramos, A. Intercalators as anticancer drugs. Curr. Pharm. Des. 2001, 7, 1745–1780.Search in Google Scholar

Braña, M. F.; Cacho, M.; Garcia, M. A.; de Pascual-Teresa, B.; Ramos, A.; Domínguez, M. T.; Pozuelo, J. M.; Abradelo, C.; Rey-Stolle, M. F.; Yuste, M.; et al. New analogues of amonafide and elinafide containing aromatic heterocycles: synthesis, antitumor activity, molecular modeling, and DNA binding properties. J. Med. Chem. 2004, 47, 1391–1399.Search in Google Scholar

Cechine Filho, V. C.; Pinheiro, T.; Nunes, R. J.; Yunes, R. A.; Cruz, A. B.; Moretto, E. Antibacterial activity of N-phenylmaleimides and related compounds. Structure-activity relationships. Il Farmaco 1994, 49, 675–677.Search in Google Scholar

Clinical and Laboratory Standards Institute. Antimicrobial Susceptibility Testing (M100-S16). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard seventh edition (M7-A7). Performance standards for antimicrobial disc susceptibility test approved standard – 9th edition (M2-A9). Clinical and Laboratory Standards Institute: Wayne, PA, 2006.Search in Google Scholar

Durante-Mangoni, E.; Grammatikos, A.; Utili, R.; Falagas, M. E. Do we still need the aminoglycosides? Int. J. Antimicrob. Agents 2009, 33, 201–205.10.1016/j.ijantimicag.2008.09.001Search in Google Scholar

Gray, A. P.; Archer, W. L.; Schlieper, D. C.; Spinner, E. E.; Cavallito, C. J. Bis-ammonium salts. Unsymmetrical derivatives of some isoquinolines and related heterocyclic bases. J. Am. Chem. Soc. 1955, 77, 3536–3541.Search in Google Scholar

Gulaid, A.; Houghton, G. W.; Lewellen, O. R.; Smith, J.; Thorne, P. S. Determination of metronidazole and its two major metabolites in biological fluids by high pressure liquid chromatography. J. Chromatogr. 1978, 6, 430–432.Search in Google Scholar

Haeberle, N.; Eberle, O. Substituted succinimides and their use as fungicides. Patent EP 46274 02 24, 1982.Search in Google Scholar

Hariprakasha, H. K.; Kosakowska-Cholody, T.; Meyer, C.; Cholody, W. M.; Stinson, S. F.; Tarasova, N. I.; Michejda, C. J. Optimization of naphthalimide-imidazoacridone with potent antitumor activity leading to clinical candidate (HKH40A, RTA 502). J. Med. Chem. 2007, 50, 5557–5560.Search in Google Scholar

Huang, S.; Norton, J.; Appella, D.; Witschi, M. Northwestern Universty, Anti-cancer compounds. Patent WO2009/89537 A2, 2009.Search in Google Scholar

Iragashi, Y.; Yagami, K.; Imai, R.; Watanabe, S. Antimicrobial activities of some N-alkylmaleimides. J. Ind. Microbiol. 1990, 6, 223–225.Search in Google Scholar

Itoh, Y.; Takeuchi, M.; Shimizu, K.; Takahashi, S.; Terahara, A.; Haneishi, T. New antibiotic, isohematinic acid. J. Antibiot. 1983, 36, 497–501.Search in Google Scholar

Kazantsev, A.; Young Anne, B.; Housman, D. Gen Hospital Corporation, Massachusetts Institute of Technology. Compositions and methods for modulating interaction betweenpolypeptides. Patent WO2005/87217 A1, 2005.Search in Google Scholar

Kuran, B.; Krawiecka, M.; Rosołowski, S.; Kossakowski, J.; Szamanek, K.; Młynarczyk, G. Synthesis and biological activity of derivatives of 1-bromo-17-azapentacyclo[6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaen-16,18-dione. Annales Sect. DDD, XXIII. 2010, 4, 19–27.Search in Google Scholar

Kuran, B.; Krawiecka, M.; Kossakowski, J.; Szymanek, K.; Kierzkowska, M.; Młynarczyk, G. Synthesis and biological activity of a novel series of 17-azapentacyclo [6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaen-16,18-dione derivatives. Acta Pol. Pharm. 2012, 5, 901–910.Search in Google Scholar

Marshall, W. F.; Blair, J. E. The cephalosporins. Mayo Clin. Proc. 1999, 74, 187–195.10.4065/74.2.187Search in Google Scholar

Mattocks, A. M.; Hutchison, O. S. S. Local anesthetics; N-dialkylaminoalkylimides of naphthalic and diphenylmaleic acids. J. Am. Chem. Soc. 1948, 70, 3474–3480.10.1021/ja01190a078Search in Google Scholar

Mukherjee, A.; Hazra, S.; Dutta, S.; Muthiah, S.; Mondhe, D. M.; Sharma, P. R.; Singh, S. K.; Saxena, A. K.; Qazi, G. N.; Sanyal, U. Antitumor efficacy and apoptotic activity of substituted chloroalkyl 1H-benz[de]isoquinoline-1,3-diones: a new class of potential antineoplastic agents. Invest. New Drugs 2011, 29, 434–442.Search in Google Scholar

Muth, M.; Bender, W.; Scharfenstein, O.; Holzgrabe, U.; Balatkova, E.; Trankle, C.; Mohr, K. Systematic development of high affinity bis(ammonio)alkane-type allosteric enhancers of muscarinic ligand binding. J. Med. Chem. 2003, 46, 1031–1040.Search in Google Scholar

Pereira, E. R.; Fabre, S.; Sancelme, M.; Prudhomme, M.; Rapp, M. Antimicrobial activities of indolocarbazole and bis-indole protein kinase C inhibitors. II. Substitution on maleimide nitrogen with functional groups bearing a labile hydrogen. J. Antibiot. 1995, 48, 863–868.Search in Google Scholar

Quaquebeke, E. V.; Mahieu, T.; Dumont, P.; Dewelle, J.; Ribaucour, F.; Simon, G.; Sauvage, S.; Gaussin, J.-F.; Tuti, J.; El Yazidi, M.; et al. 2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo [de]iso-quinolin-5-yl}carbamoyl)acetamide (UNBS3157), a novel nonhematotoxic naphthalimide derivative with potent antitumor activity. J. Med. Chem. 2007, 50, 4122–4134Search in Google Scholar

Ralph, E. D.; Kirby, W. M. M. Bioassay of metronidazole with either anaerobic or aerobic incubation. J. Infect. Dis. 1975, 132, 587–591.Search in Google Scholar

Sami, S. M.; Dorr, R. T.; Alberts, D. S.; Sólyom, A. M.; Remers, W. A. Analogues of amonafide and azonafide with novel ring systems. J. Med. Chem. 2000, 43, 3067–3073.Search in Google Scholar

Schmitz, J.; Heller, E.; Holzgrabe, U. A fast and efficient track to allosteric modulators of muscarinic receptors: microwave-assisted syntheses. Monatsh. Chem. 2007, 138, 171–174.Search in Google Scholar

Sissi, C.; Lucatello, L.; Krapcho, A. P.; Maloney, D. J.; Boxer, M. B.; Camarasa, M. V.; Pezzoni, G.; Menta, E.; Palumbo, M. Tri-, tetra- and heptacyclic perylene analogues as new potential antineoplastic agents based on DNA telomerase inhibition. Bioorg. Med. Chem. 2007, 15, 555–562.Search in Google Scholar

Takada, T.; Kawai, K.; Tojo, S.; Majami, T. Effects of interaction of photosensitizer with DNA and stacked G bases on photosensitized one-electron oxidation of DNA. J. Phys. Chem. B 2004, 108, 761–766.Search in Google Scholar

Takatori, K.; Hasegawa, T.; Nakano, S.; Kitamura, J.; Kato, N. Antifungal activities of N-substituted maleimide derivatives. Microbiol. Immunol. 1985, 29, 1237–1247.Search in Google Scholar

Tall, F. P.; Jacous, N. V.; Gorbach, S. L. In vitro activity of thienamycin. Antimicrob. Agents Chemother. 1978, 14, 436–438.Search in Google Scholar

Tian, Z. Y.; Xie, S. Q.; Du, Y. W.; Ma, Y. F.; Zhao, J.; Gao, W. Y.; Wang, C. J. Synthesis, cytotoxicity and apoptosis of naphthalimide polyamine conjugates as antitumor agents. Eur. J. Med. Chem. 2009, 44, 393–399.Search in Google Scholar

Wu, A.; Xu, Y.; Qian, X. Novel naphthalimide-amino acid conjugates with flexible leucine moiety as side chain: design, synthesis and potential antitumor activity. Bioorg. Med. Chem. 2009, 17, 592–599.Search in Google Scholar

Young, D. D.; Connelly, C. M.; Grohmann, C.; Deiters, A. Small molecule modifiers of microRNA miR-122 function for the treatment of hepatitis C virus infection and hepatocellular carcinoma. J. Am. Chem. Soc. 2010, 132, 7976–7981.Search in Google Scholar

Zee-Cheng, R. K. Y.; Cheng, C. C. N-(Aminoalky1)imide antineoplastic agents. Synthesis and biological activity. J. Med. Chem. 1985, 28, 1216–1222.Search in Google Scholar

Zejc, A.; Gorczyca, M. In Chemia Leków, Zejc, A., Ed. Antybiotyki PZWL: Warszawa, 1999; Vol. 11, pp. 600–656.Search in Google Scholar

Zentz, F.; Hellio, C.; Valla, A.; Broise De La, D.; Bremer, G.; Labia, R. Antifouling activities of N-substituted maleimides and succinimides: antibacterial activities and inhibition of Mytilys edulis phenoloxidase. Mar. Biotechnol. 2002a, 4, 431–440.Search in Google Scholar

Zentz, F.; Valla, A.; Le Guillou, R.; Labia, R.; Mathot, A. G.; Sierot, D. Synthesis and antimicrobial activities of N-substituted imides. Il Farmaco 2002b, 57, 421–426.10.1016/S0014-827X(02)01217-XSearch in Google Scholar

Zentz, F.; Le Guillou, R.; Labia, R.; Sierot, D.; Linard, B.; Valla, A. Syntheses, in vitro antibacterial and cytotoxic activities of a series of 3-substitued succinimides. Il Farmaco 2004, 59, 879–886.Search in Google Scholar

Received: 2012-8-2
Accepted: 2012-8-31
Published Online: 2012-11-12
Published in Print: 2012-12-01

©2012 by Walter de Gruyter Berlin Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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https://doi.org/10.1515/hc-2012-0115
Keywords for this article
antifungal activity; antimicrobial activity; 1H-benzo[de]isoquinoline-1,3(2H)-dione
Creative Commons
BY-NC-ND 3.0

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Research Articles
  4. Sequential amination of heteroaromatic halides with aminopyridine 1 - oxides and their N-protected derivatives based on novel aza-Smiles rearrangement
  5. Convenient synthetic route to 3-cyanopyridine-2(1H)-one derivatives with aromatic substituents
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  13. Synthesis and antimicrobial activity of derivatives of 1H-benzo[de]isoquinoline-1,3(2H)-dione
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