In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L.) chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR).

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Roth H.J., Fenner H. Arzneistoffe. 3rd Ed. Deutscher Apotheker Verlag; Stuttgart, Germany: 2000. pp. 51–114.

Polanski J., Niedbala H., Musiol R., Podeszwa B., Tabak D., Palka A., Mencel A., Finster J., Mouscadet J.F., Le Bret M. 5-Hydroxy-8-nitro-6-quinaldic Acid as a Novel Molecular Scaffold for HIV-1 Integrase Inhibitors. Lett. Drugs Des. Disc. 2006;3:175–178. doi: 10.2174/157018006776286934. DOI

Polanski J., Niedbala H., Musiol R., Podeszwa B., Tabak D., Palka A., Mencel A., Mouscadet J.F., Le Bret M. Fragment Based Approach for the Investigation of HIV-1 Integrase Inhibition. Lett. Drugs Des. Disc. 2007;4:99–105. doi: 10.2174/157018007779422532. DOI

Vargas L.Y., Castelli M.V., Kouznetsov V.V., Urbina J.M., Lopez S.N., Sortino M., Enriz R.D., Ribas J.C., Zacchino S. In vitro Antifungal Activity of New Series of Homoallylamines and Related Compounds with Inhibitory Properties of the Synthesis of Fungal Cell Wall Polymers. Bioorg. Med. Chem. 2003;11:1531–1550. doi: 10.1016/S0968-0896(02)00605-3. PubMed DOI

Jampilek J., Dolezal M., Kunes J., Buchta V. Quinaldine derivatives preparation and their antifungal activity. ECSOC-8. 2004. p. c005. Available online: http://www.lugo.usc.es/%7Eqoseijas/ECSOC-8/BOCNP/005/index.htm. PubMed

Jampilek J., Dolezal M., Kunes J., Buchta V., Kralova K. Quinaldine Derivatives: Preparation and Biological Activity. Med. Chem. 2005;1:591–599. doi: 10.2174/157340605774598108. PubMed DOI

Musiol R., Jampilek J., Buchta V., Niedbala H., Podeszwa B., Palka A., Majerz-Maniecka K., Oleksyn B., Polanski J. Antifungal Properties of New Series of Quinoline Derivatives. Bioorg. Med. Chem. 2006;14:3592–3598. doi: 10.1016/j.bmc.2006.01.016. PubMed DOI

Musiol R., Jampilek J., Kralova K., Podeszwa B., Finster J., Niedbala H., Palka A., Polanski J. New quinoline derivatives possessing herbicidal activity. ECSOC-9. 2005. p. c005. Available online: http://www.usc.es/congresos/ecsoc/9/BOCNP/c005/index.htm.

Musiol R., Jampilek J., Kralova K., Tabak D., Podeszwa B., Finster J., Polanski J. Substituted amides of quinoline derivatives: preparation and their photosynthesis-inhibiting activity. ECSOC-10. 2006. p. c007. Available online: http://www.usc.es/congresos/ecsoc/10/ECSOC10.htm.

Musiol R., Jampilek J., Kralova K., Richardson D.R., Kalinowski D., Podeszwa B., Finster J., Niedbala H., Palka A., Polanski J. Investigating Biological Activity Spectrum for Novel Quinoline Analogues. Bioorg. Med. Chem. 2007;15:1280–1288. doi: 10.1016/j.bmc.2006.11.020. PubMed DOI

Musiol R., Jampilek J., Kralova K., Tabak D., Finster J., Podeszwa B., Kozik V., Dohnal J., Polanski J. Preparation and Herbicidal Activities of Substituted Amides of Quinoline Derivatives. ECSOC-11. 2007. p. a011. Available online: http://www.usc.es/congresos/ecsoc/11/hall_aGOS/a011/index.htm.

Musiol R., Tabak D., Niedbala H., Podeszwa B., Jampilek J., Kralova K., Dohnal J., Finster J., Mencel A., Polanski J. Investigating Biological Activity Spectrum for Novel Quinoline Analogues 2: Hydroxyquinolinecarboxamides with Photosynthesis Inhibiting Activity. Bioorg. Med. Chem. 2008;16:4490–4499. doi: 10.1016/j.bmc.2008.02.065. PubMed DOI

Musiol R., Jampilek J., Kralova K., Finster J., Tabak D., Niedbala H., Csollei J., Dohnal J., Polanski J. Ring-substituted 4-hydroxy-1H-quinolin-2-ones: Preparation and Their Photosynthesis-inhibiting Activity. ECSOC-12. 2008. p. c0012. Available online: http://www.usc.es/congresos/ecsoc/12/ECSOC12.htm.

Podeszwa B., Niedbala H., Polanski J., Musiol R., Tabak D., Finster J., Serafin K., Wietrzyk J., Boryczka S., Mol W., Jampilek J., Dohnal J., Kalinowski D., Richardson D.R. Investigating the Antiproliferative Activity of Quinoline-5,8-dione Analogues on Tumour Cell Lines. Bioorg. Med. Chem. Lett. 2007;17:6138–6141. doi: 10.1016/j.bmcl.2007.09.040. PubMed DOI

Reifler M.J., Szalai V.A., Peterson C.N., Brudvig G.W. Effects of Tail-like Substituents on the Binding of Competitive Inhibitors to the QB Site of Photosystem II. J. Mol. Recognit. 2001;14:157–165. PubMed

Moreland D.E. Research on Biochemistry of Herbicides – an Historical Overview. Z. Naturforsch. C-A J. Biosci. 1993;48:121–131.

Zakarya D., Larfaoui E.M., Boulaamail A., Tollabi M., Lakhlifi T. QSARs for a Series of Inhibitory Anilides. Chemosphere. 1998;36:2809–2818. doi: 10.1016/S0045-6535(97)10239-9. DOI

Kralova K., Sersen F., Kubicova L., Waisser K. Inhibitory Effects of Substituted Benzanilides on Photosynthetic Electron Transport in Spinach Chloroplasts. Chem. Pap. 1999;53:328–331.

Dolezal M., Miletin M., Kunes J., Kralova K. Synthesis and Biological Evaluation of Some Amides of Pyrazine-2-carboxylic acids. Molecules. 2002;7:363–373. doi: 10.3390/70300363. DOI

Dolezal M., Palek L., Vinsova J., Buchta V., Jampilek J., Kralova K. Substituted Pyrazinecarboxamides: Synthesis And Biological Evaluation. Molecules. 2006;11:242–256. doi: 10.3390/11040242. PubMed DOI PMC

Dolezal M., Cmedlova P., Palek L., Vinsova J., Kunes J., Buchta V., Jampilek J., Kralova K. Synthesis and Antimycobacterial Evaluation of Substituted Pyrazinecarboxamides. Eur. J. Med. Chem. 2008;43:1105–1113. PubMed

Polak A. The past, Present and Future of Antimycotic Combination Therapy. Mycoses. 1999;42:355–370. doi: 10.1046/j.1439-0507.1999.00475.x. PubMed DOI

Fostel J.M., Lartey P.A. Emerging Novel Antifungal Agents. Drug Discov. Today. 2000;5:25–32. doi: 10.1016/S1359-6446(99)01430-0. PubMed DOI

[accessed on January 30, 2009]. Available online: http://www.doctorfungus.org/

Gershon H, Gershon M, Clarke D.D. Synergistic Mixtures of Fungitoxic Monochloro- and Dichloro-8-quinolinols against Five Fungi. Mycopathologia. 2004;158:131–135. doi: 10.1023/B:MYCO.0000038427.42852.6a. PubMed DOI

Dardari Z., Lemrani M., Bahloul A., Sebban A., Hassar M., Kitane S., Berrada M., Boudouma M. Antileishmanial Activity of a New 8-Hydroxyquinoline Derivative Designed 7-[5′-(3′-phenylisoxazolino)methyl]-8-hydroxyquinoline: preliminary study. Farmaco. 2004;59:195–199. doi: 10.1016/j.farmac.2003.11.001. PubMed DOI

Sheehan D.J., Espinel-Ingroff A., Steele M., Webb C.D. Antifungal Susceptibility Testing of Yeasts: a Brief Overview. Clin. Infect. Dis. 1993;17:494–500. doi: 10.1093/clinids/17.Supplement_2.S494. PubMed DOI

Dolezal M., Jampilek J., Osicka Z., Kunes J., Buchta V., Vichova P. Substituted 5-aroylpyrazine-2-carboxylic Acid Derivatives: Synthesis and Biological Activity. Farmaco. 2003;58:1105–1111. doi: 10.1016/S0014-827X(03)00163-0. PubMed DOI

Collins J.F., Donnelly W.J., Grundon M.F., James K.J. Biosynthesis of Aromatic Isoprenoids. Part I. The role of 3-Prenylquinolines and of Platydesmine in the Biosnthesis of the Furuquinoline Alkaloid, Dictamnine. J. Chem. Soc., Perkin Trans. 1974;1:2177–2181.

Buckle D.R., Cantello B.C.C., Smith H., Spicer B.A. 4-Hydroxy-3-nitro-2-quinolones and Related Compounds as Inhibitors of Allergic Reactions. J. Med. Chem. 1975;18:726–732. doi: 10.1021/jm00241a017. PubMed DOI

Ziegler E., Wolf R., Kappe T. Synthesen von Heterocyclen, 66. Mitt.: Eine Einfache Synthese des 4-Hydroxycarbostyrils und seiner Derivate. Monatsh. Chem. 1965;96:418–422. doi: 10.1007/BF00909449. DOI

Dolle V., Fan E., Nguyen C.H., Aubertin A.M., Kirn A., Andreola M.L., Jamieson G., Tarrago-Litvak L., Bisagni E. A New Series of Pyridinone Derivatives as Potent non-Nucleoside Human Immunodeficiency Virus Type 1 Specific Reverse Transcriptase Inhibitors. J. Med. Chem. 1995;38:4679–4686. doi: 10.1021/jm00023a007. PubMed DOI

Ukrainets I.V., Taran S.G., Sidorenko L.V., Gorokhova O.V., Ogirenko A.A., Turov A.V., Filimonova N.I. 4-Hydroxy-2-quinolones. 3-Amino-1-R-2-oxo-4-hydroxyquinolines and Their Acyl Derivatives. Chem. Heterocycl.Compd. 1996;32:960–970. doi: 10.1007/BF01176974. DOI

Ukrainets I.V., Gorokhova O.V., Sidorenko L.V. 4-Hydroxyquinol-2-ones. 85. Synthesis of 2-Chloro-4-hydroxyquinoline-3-carboxylic Acid Ethyl Ester. Chem. Heterocycl. Compd. 2005;41:1019–1021. doi: 10.1007/s10593-005-0271-8. DOI

Detsi A., Bardakos V., Markopoulos J., Igglessi-Markopoulou O. Reactions of 2-Methyl-3,1-benzoxazin-4-one with Active Methylene Compounds: a New Route to 3-Substituted 4-Hydroxyquinolin-2(1H)-ones. J. Chem. Soc., Perkin Trans. 1. 1996;24:2909–2913.

Masarovicova E., Kralova K. Approaches to Measuring Plant Photosynthesis Activity. In: Pessarakli M., editor. Handbook of Photosynthesis. 2nd Ed. Taylor & Francis Group; Boca Raton, London-New York-Singapore: 2005. pp. 617–656.

Kralova K., Sersen F., Sidoova E. Photosynthesis Inhibition Produced by 2-Alkylthio-6-R-benzothiazoles. Chem. Pap. 1992;46:348–350.

Fedke C. Biochemistry and Physiology of Herbicide Action. Springer Verlag; Berlin-Heidelberg-New York, USA : 1982.

National Committee for Clinical Laboratory standards . Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast: Approved Standard, NCCLS document M27-A. NCCLS; Villanova, PA, USA: 1997.

The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot †

Microwave-assisted synthesis of new substituted anilides of quinaldic acid

Investigating the spectrum of biological activity of substituted quinoline-2-carboxamides and their isosteres

Synthesis and characterization of (Z)-5-arylmethylidene-rhodanines with photosynthesis-inhibiting properties

Investigating the spectrum of biological activity of ring-substituted salicylanilides and carbamoylphenylcarbamates

Investigating biological activity spectrum for novel styrylquinazoline analogues