New antihyperglycemic, α-glucosidase inhibitory, and cytotoxic derivatives of benzimidazoles
| Autor: | Jaladi Ashok Kumar, Kuncha Madhusudhana, Boreddy Srinivas Reddy, Sistala Ramakrishna, Ashok Kumar Tiwari, Bhimapaka China Raju, Amtul Z. Ali |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Benzimidazole Magnetic Resonance Spectroscopy Spectrophotometry Infrared Glycoside Hydrolase Inhibitors Antineoplastic Agents Saccharomyces cerevisiae Mass Spectrometry chemistry.chemical_compound Cell Line Tumor Drug Discovery Animals Humans Hypoglycemic Agents Cytotoxic T cell Enzyme Inhibitors Rats Wistar IC50 Pharmacology chemistry.chemical_classification biology General Medicine Yeast Rats Enzyme chemistry Biochemistry Alpha-glucosidase Cell culture biology.protein Benzimidazoles |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry. 25:80-86 |
| ISSN: | 1475-6374 1475-6366 |
| DOI: | 10.3109/14756360903017122 |
| Popis: | Glycosidases play an important role in a wide range of physiological and pathological conditions, and have become potential targets for the discovery and development of agents useful for the treatment of diseases such as diabetes, cancer, influenza, and even AIDS. In this study, several benzimidazole derivatives were prepared from o-phenylenediamine and aromatic and heteroaromatic carboxaldehydes in very good yields, using PdCl2(CH3CN)2 as the most efficient catalyst. Synthesized compounds were assayed for their activity on yeast and rat intestinal alpha-glucosidase inhibition and cytotoxic activity against colon carcinoma cell line HT-29. Compound 3e exhibited 95.6% and 75.3% inhibition of yeast and rat intestinal alpha-glucosidase enzyme, while showing 74.8% cytotoxic activity against the HT-29 cell line at primary screening concentrations of 2.1 mM for yeast and rat intestinal alpha-glucosidase enzyme and 0.2 mM for cytotoxic activity against the HT-29 cell line, respectively. Compound 3c displayed 76% and 34.4% inhibition of yeast and rat intestinal alpha-glucosidase enzyme, and 80.4% cytotoxic activity against the HT-29 cell line at similar primary screening concentrations. The IC50 value for the most potent intestinal alpha-glucosidase inhibitor compound 3e was found to be 99.4 microM. The IC50 values for the most active cytotoxic compounds 3c and 3e were 82 microM and 98.8 microM, respectively. Both compounds displayed significant antihyperglycemic activity in starch-induced postprandial hyperglycemia in rats. This is the first report assigning yeast and rat intestinal alpha-glucosidase enzyme inhibition, cytotoxic activity against the HT-29 cell line, and antihyperglycemic activity to benzimidazole compounds 3c and 3e. |
| Databáze: | OpenAIRE |
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