Previously we described a significant tuberculostatic activity of some 2-phenalkyl- and 2-cyclohexylalkylbenzimidazoles [1]. Then we reported synthesis and activity of 2-(2-cyclohexylethyl)-1H-benzo[d]imidazoles analogues with benzimidazole type of structure. Their tuberculostatic activity in vitro was at the level appropriate for the administrated chemotherapeutics [2]. Here we disclosed the synthesis of novel 2-(2-phenalkyl)-1H-benzo[d]imidazoles. We synthesized structures with different substituents at the benzene ring of benzimidazole system, styryl, phenethyl or 3,5-dichlorophenethyl moiety at C-2 position.

Target benzimidazoles were obtained by two different methods. In one of them appropriate carboxylic acids were heated with o-phenylenediamine derivatives in metal bath. In the another synthesis result was reached in two steps, substitution in order to get the amid and cyclization to benzimidazole system. All the newly synthesized compounds were characterized by IR, ¹H NMR, and ¹³C NMR spectra. They have been also tested for tuberculostatic activity in vitro against M. tuberculosis strains. Their cytotoxic activity towards eukaryotic cells was also evaluated.

As a result of the synthesis twelve novel derivatives of 2-(2-phenylalkyl)-1H-benzo[d]imidazole have been obtained. Some of the compounds exhibited very good activity towards M. tuberculosis sensitive and resistant “wild” strains and the standard strain. Cytotoxicity studies indicated differential toxicity of these compounds against eukaryotic cells. Obtained results suggest that some of the synthesized compounds are good candidates for tuberculosis drugs. These compounds have a good therapeutic potential.

This study is supported by the National Science Centre, Cracow (grant no. 2011/0 1/B/NZ4/01187).

References:

[1] H. Foks, D. Pancechowska-Ksepko, W. Kuźmierkiewicz, Z. Zwolska, E. Augustynowicz-Kopeć, M. Janowiec: Synthesis and Tuberculostatic Activity of New Benzimidazole Derivatives, Chem. Heterocycl. Compd., 42 (2006) 697–700.

[2] K. Gobis, H. Foks, K. Bojanowski, E. Augustynowicz-Kopeć, A. Napiórkowska: Synthesis of novel 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds and their evaluation for tuberculostatic activity, Bioorg. Med. Chem. 20 (2012) 137-144.

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1. Novel N-substituted 2-(2-phenalkyl)-1H-benzo[d]imidazoles: synthesis, characteristics and tuberculostatic activity
2. Synthesis and tuberculostatic activity of novel 2-(2-cyclohexylethyl)-1H-benzo[d]imidazoles
3. Synthesis and antifungal activity of novel S-esters and S,S'-diesters of N'-(2-hydroxybenzoyl) hydrazinecarbo- dithioic acids
4. Synthesis and tuberculostatic activity of new N’-(6-methoxypyrazine-2-carbonyl)dithiocarbazic acid esters and their amidrazone analogs
5. Formation of 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside triphosphate in the Erythrocytes, Endothelium and Cardiomyocytes and its Effect on ATP Concentration
6. THE IMPORTANCE OF THE TYPE OF ISONIAZID ACETYLATION IN MONITORING OF TUBERCULOSIS TREATMENT.
7. SYNTHESIS AND ANTITUBERCULOUS ACTIVITY OF NEW 3,5-DISUBSTITUTED- 1,2,4-OXADIAZOLES
8. NEW 3-ALKENYL DERIVATIVES OF RIFAMYCIN ANTIBIOTICS