Bazı yeni N-sübstitüe-benzimidazole-5(6)-sülfonamid türevlerinin sentezi, yapı-aydınlatmaları ve antimikrobiyal etkileri ve kantitatif yapı-etki ilişkileri analizi
Özet
In this study, uncommercial starting materials were prepared by the literature methods, for this purpose, N-substituted sulphonamides on the C-5(6) position were prepared by the reaction between 4-chloro-3-nitrobenzensulphonyl chloride and corresponding amines, then, chlorine atom was converted to amines by using the aromatic nucleophilic substitution reaction. The Pd/C catalyzed reduction of 2, 3 and 6 gave 3,4-diaminobenzen-5(6)- sulphonamides (4, 5, 7). o-Phenylenediamin-5(6)-sulphonic acide was prepared by two different methods. At the first method, 4-chloro-3-nitrobenzensulphonyl chloride was converted to sulphonic acid, then, chlorine atom was transformed to amines. The Pd/C catalyzed reduction of 9 gave 3,4-diaminobenzen-5(6)-sulphonic acides (10). In the second method, o-phenylendiamine was directly treated with fuming H2SO4, at high temparature. 3- [5,6-dichloro-1-(4-chlorobenzyl)-1H-benzimidazole-2-il]benzensulphonic acide was prepared with 1,2,4-trichloro-5-nitrobenzen as starting material. The final compounds (16 - 41) were obtained by the condensation of substituted-o-phenylendiamines (4, 5, 7, 10, 12) with Na2S2O5 adduct of arylaldehydes (K1-11) in DMF. Compound 41 was converted to acylchloride with SOCl2, then acylchlorides were converted to targeted amide derivatives, 42-44. A series of novel 34 and 10 known compounds were prepared in this study. The purity of these compounds were checked with their melting points and TLC. The chemical structure of the compounds were elucidated with their , 1H-NMR, 13C-NMR, 19F-NMR, 2D- (NOESY, gCOSY, gHSQC, gHMBC, DEPT) and Mass (ESI+, ESI-) spectral data and their elemantel analysis. The in vitro antibacterial activity of the synthesized compounds against S. aureus ATCC 25923 were evaluated by the Macrodilution Broth and Disc Diffusion Techniques as well. Some of the compounds exhibited more potent inhibitory activity against the selected bacteria than reference compounds ampicilline and sultamicilline. The most active compounds 37 and 38 have the lowest MIC values with 0.39 ?g/ml. In addition, the compounds having sulfonamido moities (Compounds 22, 29 and 31) have important inhibitory activity with 1.56 ?g/ml value. In order to explain the quantitative structure activity relationship between the synthesized 9 compounds and their inhibitory activities against S. aureus, several parameters have been used