Browsing by Author "Alp, Mehmet"

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    N-Sübstitüe amidin grubu taşıyan bazı heterosiklik halkaların sentez, yapı-aydınlatmaları ve antimikrobial etkileri üzerinde çalışmalar
    (Sağlık Bilimleri Enstitüsü, 2001) Alp, Mehmet; Göker, Hakan; Eczacılık
    76 SUMMARY Studies on the Synthesis, Structure Elucidation of Some N-Substituted Heterocyclic Rings Having Carboxamidine Group and Evaluation of Their Antimicrobial Activities In this study, 5 new targeted of N-sübstituted-2-(sübstituted-phenyl)-lH- benzimidazole-5(6)-carboxamidine (3a-3e) were prepared by using Pinner reaction. First, 4-amino-3-nitrobenzonitrile was reduced to 3,4-diaminobenzo- nitrile (1) with H2, Pd / C in Parr apparatus. Then, the reaction of 1 with the sodiummetabisulfite adduct of appropriate aldehydes in dimethylformamide realised benzimidazole cyclization (2a-c). Nitril group of these compounds were converted to imidate ester by using anhydrous ethanol and hydrogen chloride gas which was dried over sulphiric acid. Then these unstable esters were immediately transform into to the requested 5(6)-carboxamidine benzimidazole derivatives (3a-3e). In this study, 5 new targeted compounds as well as 3 intermediates were prepared for the first time by the given reactions above. The purity of the synthesized compounds were controlled by thin layer chromatography and melting points were determined and uncorrected. The chemical structure of the compounds were elucidated by their Infrared, Nuclear Magnetic Rezonans, Mass spectral data and their elemental analysis results. The in vitro antifungal activity of the synthesized compounds against Candida albicans were evaluated by the Disc Diffusion Techniques. Among them compound 3c, showed close activity with 21 mm inhibition zone to the reference compound Miconazole. Key Words : Amidine Derivatives, Benzimidazole Nitril Derivatives, lH-Benzimidazole Carboxamidine Derivatives, Synthesis and Structure Elucidation, Antifungal Activity.
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    N-Sübstitüe Amidin Grubu Taşıyan Benzimidazol Türevi Bileşiklerin Sentez, Yapı Aydınlatmaları ve Antimikrobiyal Etkileri Üzerinde Çalışmalar.
    (Sağlık Bilimleri Enstitüsü, 2007) Alp, Mehmet; Göker, Hakan; Eczacılık
    In this study, at the first step, 4-amino-3-nitrobenzonitrile was converted to imidate ester by using anhydrous ethanol with saturated dry HCl gas, followed by the unstable ester was immediately converted to 4-amino-3-nitrobenzamidine (1) with passing through NH3 gas in ethanol. The Pd/C catalyzed reduction of 1 gave 3,4-diaminobenzamidin (2). Benzimidazol cyclization was performed by heating 2 with the 3,4-dinitrobenzoic acid in polyphosphoric acid, and 2-(3,4-dinitrophenyl)-benzimidazole 5-carboxamidine was obtained (3). Reduction of both nitro group yielded 2-(3,4-diaminophenyl) benzimidazole-5-carboxamidine (4). Condensation of 4-chlorophenol with 2-fluorobenzaldehyde, 4-fluorobenzaldehyde, 2,5-difluoro-benzaldehyde; and 3,4-dimetoxyphenol with 4-fluorobenzaldehyde yielded the corresponding substitue-phenyloxybenzaldehydes (5-8). The final compounds (9-26) were obtained by condensation of 2-(3,4-diaminophenyl)-benzimidazole-5(6)-carboxamidine (4) with Na2S2O5 adduct of 5-8 and commercial arylaldehydes in DMF. A series of novel 18 final compounds (with 2 novel and 6 known intermediates) was prepared in this study. The purity of these compounds was checked with their melting points, TLC and tR retentation times in reverse phase HPLC. The chemical structures of the compounds were elucidated with their 1H-NMR, 13C-NMR, 19F-NMR, 2D-COSY, 2D-HSQC spectrum, Mass (ESI+) spectral data and their elemantel analysis. The synthesized compounds (9-26) were screened for their in vitro activity against four parasitic protozoa, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. The medium-throughput screening method was used to test the compouds at two concentrations, 0.81 ?M and 4.85 ?M, respectively. According to medium-throughput screening results, all compounds have significant inhibitory activity against P. falciparum and thirteen of them have remarkable inhibitory activity against T. b. rhodesiense at low concentration, its IC50 values were determined. On the other hand, none of these compounds displayed appreciable inhibitory activity against T. cruzi and L. donovani, therefore not further investigated to determine their IC50 values. The in vitro antifungal activity of the synthesized compounds against Candida albicans and Candida krusei is evaluated with Macrodilution Techniques. The cytotoxic potentials of these compounds on mammalian (rat skeletal muscle myoblast, L6) cells were also assessed and compared to that of podophyllotoxin. Compound 10, 17 and 24, with IC50 values of 0.041, 0.06 and 0.036 ?g/ml respectively, are the most active monocation against T. b. rhodesiense. The most potent antiplasmodial compounds, 9, 10, 17, showed IC50 values as 0.007, 0.010 and 0.008 ?g/ml respectively. Compound 25 (IC50 = 0.78 ?g/ml) and 12 (IC50 = 1.56 ?g/ml) were highly effective against C. albicans. Compounds 13 and 24 exhibited the best antifungal activity against C. krusei with IC50 value of 6.25 ?g/ml. In general, there was good selectivity for the parasitic organisms by synthesized compounds (9-26) as judged from their cellulary cytotoxicity. In order to explain the quantitative structure activity relationship between the synthesized compounds and their inhibitory activities against the selected protozoa and fungi, several parameters have been used. The best correlation was found with Log P values of the synthesized compounds against T. b. rhodesiense.
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    Synthesis and potent antimicrobial activity of some novel N-(Alkyl)-2-phenyl-1H-benzimidazole-5-carboxamidines
    (2005) Alp, Mehmet; Yıldız, Sulhiye; Göker, Hakan; Eczacılık Fakültesi
    A series of 22 novel 1,2-disubstituted-1H-benzimidazole-N-alkylated-5-carboxamidine derivatives were synthesized and evaluated for in vitro antibacterial activity against S. aureus and methicillin resistant S. aureus (MRSA), E. coli, E. faecalis and for antifungal activity against C. albicans. Compound 59 [1-(2,4-dichlorobenzyl)-N-(2-diethylaminoethyl)-1H-benzimidazole-5-carboxamidine], with a 3,4-dichlorophenyl group at the C-2 position, displayed the greatest activity (MIC = 3.12 mu g/mL against both some bacteria and the fungus C. albicans).
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    Synthesis and Potent Antimicrobial Activity of Some Novel N-(Alkyl)-2-Phenyl-1H-Benzimidazole-5-Carboxamidines
    (2005) Göker, Hakan; Alp, Mehmet; Yıldız, Serap Süzük; Eczacılık Fakültesi
    A series of 22 novel 1,2-disubstituted-1H-benzimidazole-N-alkylated-5-carboxamidine derivatives were synthesized and evaluated for in vitro antibacterial activity against S. aureus and methicillin resistant S. aureus (MRSA), E. coli, E. faecalis and for antifungal activity against C. albicans. Compound 59 [1-(2,4-dichlorobenzyl)-N-(2-diethylaminoethyl)-1H-benzimidazole-5-carboxamidine], with a 3,4-dichlorophenyl group at the C-2 position, displayed the greatest activity (MIC = 3.12 μg/mL against both some bacteria and the fungus C. albicans).