Synthesis and biological activities of new substituted thiazoline-quinoline derivatives

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Synthesis and biological activities of new substituted thiazoline-quinoline derivatives

5-Acyl-8-hydroxyquinoline-2-(3'-substituted-4'-aryl-2,3-dihydrothiazol-2'-ylidene)hydrazones, 5a-e to 10a-c, were prepared by the reaction of appropriate 5-acyl-8-hydroxyquinoline-4-substituted thiosemicarbazones 3a-e and phenacyl bromides 4a-e. Structures of the new compounds were verified on the basis of spectral and elemental analyses. Twenty-eight new compounds were tested for their possible antimicrobial activities. Most of the tested compounds showed weak to moderate antibacterial activity against most of the bacterial strains used in comparison with gatifloxacin as a reference drug. The test compounds showed weak to moderate antifungal activity against tested fungi in comparison with ketoconazole as a reference drug. On the other hand, the newly synthesized compounds were tested for their anti-inflammatory effects and most of them showed good to excellent anti-inflammatory activity compared to indomethacin. Moreover, ulcerogenicity and the median lethal dose (LD50) of the most active anti-inflammatory compounds 6b and 9e were determined in mice; they were non-toxic at doses up to 400 mg kg-1 after i.p. administration.

S. G. Abdel-Moty, M. H. Abdel-Rahman, H. A. Elsherief and A. H. N. Kafafy, Synthesis of some quinoline thiosemicarbazone derivatives of potential antimicrobial activity, Bull. Pharm. Sci. (Assiut University) 28 (2005) 79-93.

R. Vlahov, St. Parushev, J. Vlahov, P. Nickel and G. Snatzke, Synthesis of some new quinoline derivatives - potential antimalarial drugs, Pure Appl. Chem. 62 (1990) 1303-1306; DOI: 10.1351/pac199062071303.

M. Normand-Bayle, C. Bénard, V. Zouhiri, J. Mouscadet, H. Leh, C. Thomas, G. Mbemba, D. Desmaële and J. d'Angelo, New HIV-1 replication inhibitors of the styryquinoline class bearing aroyl/acyl groups at the C-7 position: synthesis and biological activity, Bioorg. Med. Chem. Lett. 15 (2005) 4019-4022; DOI: 10.1016/j.bmcl.2005.06.036.

S. T. Hazeldine, L. Polin, J. Kushner, K. White, T. H. Corbett, J. Biehl and J. P. Horwitz, Part 3: Synthesis and biological evaluation of some analogs of the antitumor agents, 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid, and 2-{4-[7-bromo-2-quinolinyl)-oxy]phenoxy}propionic acid, Bioorg. Med. Chem. 13 (2005) 1069-1081, DOI: 10.1016/j.bmc.2004.11.034.

J. He, L. Yun, R. Yang, Z. Xiao, J. Cheng, W. Zhou and Y. Zhang, Design, synthesis, and biological evaluation of novel 4-hydro-quinoline-3-carboxamide derivatives as an immunomodulator, Bioorg. Med. Chem. Lett. 15 (2005) 2980-2985; DOI: 10.1016/j.bmcl.2005.04.040.

D. V. Kravchenko, V. V. Kysil, A. P. Ilyn, S. E. Tkachenko, S. Maliarchouk, I. M. Okun and A. V. Ivachtchenko, 1,3-Dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines as potent caspase-3 inhibitors, Bioorg. Med. Chem. Lett. 15 (2005) 1841-1845; DOI: 10.1016/j.bmcl.2005.02.027.

Z. Dardari, M. Lemrani, A. Bahloul, A. Sebban, M. Hassar, S. Kitane, M. Berrada and M. Boudouma, Antileishmanial activity of a new 8-hydroxyquinoline derivative designed 7-[5-(3'-phenylisoxazolino)methyl]-8-hydroxyquinoline: preliminary study, Farmaco 59 (2004) 195-199; DOI: 10.1016/j.farmac.2003.11.001.

F. E. Goda, A. A. Abdel-Aziz and H. A. Ghoneim, Synthesis and biological evaluation of novel 6-nitro-5-substituted aminoquinolines as local anesthetic and anti-arrhythmic agents: molecular modeling study, Bioorg. Med. Chem. 13 (2005) 3175-3183; DOI: 10.1016/j.bmc.2005.02.050.

L. Savini, L. Chiasserini, C. Pellerano, W. Filippelli and G. Falcone, Synthesis and pharmacological activity of 1,2,4-triazolo[4,3-a]quinolines, Farmaco 56 (2001) 939-945; DOI: 10.1016/S0014-827X(01)01166-1.

A. M. Omar, I. C. Ahmed, A. M. Hassan, O. M. AboulWafa, H. Abou-Shleib and K. A. Ismail, Synthesis and evaluation for antibacterial and antifungal activities of new 1-phenylhydrazono-2-(substituted thiocarbamoyl)hydrazonopyruvaldehyde and the corres- ponding thiazoline and thiazolidinone derivatives, Alex. J. Pharm. Sci. 4 (1990) 182-186.

D. L. Klayman, J. P. Scovill, J. Bruce and J. F. Bartosevich, 2-Acetylpyridine thiosemicarbazones, 8. Derivatives of 1-acetylisoquinoline as potential antimalarial agents, J. Med. Chem. 27 (1984) 84-87; DOI: 10.1021/jm00367a018.

S. Sharma, F. Athar, M. R. Maurya, F. Naqvi and A. Azam, Novel bidentate complexes of Cu(II) derived from 5-nitrofuran-2-carboxaldehyde thiosemicarbazones with antiamoebic activity against E. histolytica, Eur. J. Med. Chem. 40 (2005) 557-562, DOI: 10.1016/j. ejmech.2005.01.003.

H. Y. Hassan, Synthesis and chelating properties of substituted formyl pyridine thiosemicarbazones of potential biological activity, Bull. Pharm. Sci. (Assiut University) 22 (1999) 97-108.

S. M. Sondhi, N. Singh, A. M. Lahoti, K. Bajaj, A. Kumar, O. Lozach and L. Meijer, Synthesis of acridinyl-thiazolino derivatives and their evaluation for anti-inflammatory, analgesic and kinase inhibition activities, Bioorg. Med. Chem. 13 (2005) 4291-4299; DOI: 10.1016/j.bmc.2005.04.017.

G. Mahler, G. Serra, S. Dematteis, J. Saldaña, L. Domínguez and E. Manta, Synthesis and biological evaluation of simplified mycothiazole analogues, Bioorg. Med. Chem. Lett. 16 (2006) 1309-1311; DOI: 10.1016/j.bmcl.2005.11.072.

M. Shih and F. Ke, Synthesis and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives, Bioorg. Med. Chem. 12 (2004) 4633-4643; DOI: 10.1016/j.bmc.2004.06.033.

D. Barton and W. D. Ollis, Comprehensive Organic Chemistry (Ed. D. N. Jones), Vol. 3, Pergamon Press, New York 1979, p. 453.

A. I. Vogel, A. R. Tatchell, B. S. Furnis, A. J. Hannaford, P. W. G. Smith, Vogel's Textbook of Practical Organic Chemistry, 5th ed, Harlow Pearson Ed. Ltd. 1989, p. 1052.

W. Hewitt, An Introduction to Quantitative Principles and Evaluation, in Microbiological Assay, Academic Press, New York 1977.

B. Tan, Guidelines on the Care and Use of Animals for Scientific Purposes, National Advisory Committee for Laboratory Animals, Singapore 2004.

L. V. Nargund, G. R. Reddy and V. Hariprasad, Anti-inflammatory activity of substituted 1,3,4-oxadiazoles, J. Pharm. Sci. 83 (1994) 246-248; DOI: 10.1002/jps.2600830226.

H. Ikuta, H. Shirota, S. Kobayashi, Y. Yamagishi, K. Yamada, I. Yamatsu and K. Katayama, Synthesis and anti-inflammatory activities of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones, J. Med. Chem. 30 (1987) 1995-1998.

F. Sztaricskai, I. E. Takács, F. Pusztai, G. Szabó and I. Csípõ, Antiulcer effect of the N-and O-β-D-glucopyranosides of 5-aminosalicylic acid, Arch. Pharm. Pharm. Med. Chem. 332 (1999) 321-326.

J. Leo, Calculating log Poct from structures, Chem. Rev. 93 (1993) 1281-1306; DOI: 10.1021/cr00020a001.

G. Dannhardt, W. Kiefer, G. Krämer, S. Maehrlein, U. Nowe and B. Fiebich, The pyrrole moiety as a template for Cox-1/Cox-2 inhibitors, Eur. J. Med. Chem. 35 (2000) 499-510; DOI: 10.1016/S0223-5234(00)00150-1.

M. J. O'Neil, A. Smith, P. E. Heckelman and S. Budavari (Eds), The Merck Index:, 13th ed, Merck Inc., Whitehouse Station (NJ) 2001, p. 892.

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