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Synthesis, Characterization and Biological Evaluation of Benzimidazole Derivatives as Potential Anxiolytics
Considerable attention has been focused on the synthesis of benzimidazoles due to their broad spectrum of biological activities such as antimicrobial, anti diabetic, anti cancer, anti hypertensive, anti anxiolytic and inflammatory activities etc. As a part of our research work, a series of benzimidazole derivatives were synthesized in good to high yields by reaction of o-phenylenediamine and different aromatic aldehydes in the presence of ammonium chloride (NH4Cl), as an efficient catalyst at room temperature. This environmentally safe and practical method offers several advantages, such as high yields, use of an available catalyst, mild reaction conditions and easy work-up process. All synthesized compounds were characterized by detailed spectral analysis by using LC-MS, IR, and NMR spectroscopy. The synthesized benzimidazoles were screened for chronic anti anxiety activity in albino rats by using light and dark box model with standard Buspirone. Behavioral parameters were recorded during the test session of 5 minutes. All benzimidazole derivatives have shown significant anti anxiety activity compared to the standard. However, benzimidazole analog (3e) exhibited highest anxiolytic action.
Aromatic Aldehydes, Ammonium Chloride, O-Phenylenediamine, Room Temperature, Light and Dark Box Apparatus, Buspirone.
- Norman G Brink, Karl. Folkers, 5, 6-Dimethylbenzimidazole-a Degradation Product of Vitamin B12. J. Am. Chem. Soc., 1949; 71(18):2951.
- Lazer ES, Matteo MR, Possanza GJ. Benzimidazole Derivatives with Atypical Antiinflammatory Activity. J. Med.Chem., 1987;729(solvent C):726–9.
- Tong Y, Bouska JJ, Ellis PA, Johnson EF, Leverson J, Liu X, et al. Synthesis and Evaluation of New Generation of Orally Efficacious Benzimidazole-Based Poly (ADP-ribose) Polymerase-1 (PARP-1) Inhibitors as Anticancer Agents. J. Med.Chem. 2009; 52(21):6803–13.
- Lee-dutra A, Arienti KL, Buzard DJ, Hack MD, Khatuya H, Desai PJ, et al. Identification of 2-arylbenzimidazoles as potent human histamine H 4 receptor ligands. Bioorg. Med. Chem Lett.2006; 16: 6043–48.
- Katiyar SK, Gordon VR, Mclaughlin GL, Edlind TD. Antiprotozoal Activities of Benzimidazoles and Correlations with 13-Tubulin Sequence. Antimicrob. Agents. Chemother. 1994; 38 (9): 2086–90.
- Youssef AM, Malki A, Badr MH, Elbayaa RY, Sultan AS. Synthesis and Anticancer Activity of Novel Benzimidazole and Benzo- thiazole Derivatives against HepG2 Liver Cancer Cells.Medicinal Chemistry., 2012; 8 (02):151–62.
- Cloarecr A. Cardiotonic Agents. Synthesis and Cardiovascular Properties. .J. Med. Chem, 1992; 35 (23): 4455-63.
- Tanaka J, Iida H, Abe M, Yuda Y, Inoue S, Gastric Antisecretory and Anti-ulcer Effect of ME3407, a New Benzimidazole Derivative, in Rats. Arzneim.-Forsch./Drug Res., 54(4):2004; 229.
- El-Gohary NS, Shaaban MI. Synthesis and biological evaluation of a new series of benzimidazole derivatives as antimicrobial, antiquorum-sensing and antitumor agents. European Journal of Medicinal Chemistry. Elsevier Masson SAS; 2017; 131: 255–62. Available from: http: // linkinghub. elsevier. Com / retrieve/ pii/ S0223523417301757
- Sharma MC, Kohli D V, Sharma S, Sharma AD, Mahavidyalya Y. Synthesis and antihypertensive activity of some new benzimidazole biphenyl-2-carboxylic acid in the presences of BF 3 · OEt 2. Der Pharmacia Sinica, 2010; 1 (1):104–115.
- Arshad T, Khan KM, Rasool N, Salar U, Hussain S, Asghar H, et al. 5-Bromo-2-aryl benzimidazole derivatives as noncytotoxic potential dual inhibitors of α -glucosidase and urease enzymes. Bioorganic Chemistry [Internet]. 2017; 72: 21–31.
- Nadeem Siddiqui et al, Antidepressant, Analgesic Activity and SAR Studies of Substituted Benzimidazoles. Asian. J. Pharm. Res, 2016; 6 (3): 170-174.
- Richter HGF, Benson GM, Bleicher KH, Blum D, Chaput E, Clemann N, et al. Bioorganic & Medicinal Chemistry Letters Optimization of a nov class of benzimidazole-based farnesoid X receptor ( FXR ) agonists to improve physicochemical and ADME properties. Bioorganic & Medicinal Chemistry Letters [Internet]. Elsevier Ltd; 2011; 21(4):1134–40. Available from: http://dx.doi.org/10.1016/j.bmcl.2010.12.123
- López SE, Restrepo J, Pérez B, Ortiz S, Salazar J. One Pot Microwave Promoted Synthesis of 2-Aryl-1 H -Benzimidazoles Using Sodium Hydrogen Sulfite. Bull. Korean Chem.Soc., 2009; 30 (7):1628–30.
- Pradeep Kumar et al, Synthesis and Pharmacological Evaluation of Some New 2-Phenyl benzimidazoles Derivatives and their Schiff’ s Bases. E-Journal of Chemistry, 2009;6(S1):342–7.
- López SE, Rosales ME, Urdaneta N, Godoy MV, Charris JE. The synthesis of substituted 2-aryl 4 (3H ) - quinazolinones using NaHSO 3 / DMA. The steric effect upon the cyclisation-dehydrogenation step. J. Chem. Res, 2000; (S): 258–9.
- K. Bahrami et al., A Simple and Efficient One-Pot Synthesis of 2-Substituted Benzimidazoles. Synthesis, 2007; 4: 547-550.
- Yang A, Fokas D, Li J, Yu L, Baldino CM. A Versatile Method for the Synthesis of Benzimidazoles from o -Nitroanilines and Aldehydes in One Step via a Reductive Cyclization. Synthesis, 2005; 1: 47-56.
- Lin S, Yang L. A simple and efficient procedure for the synthesis of benzimidazoles using air as the oxidant. Tetrahedron letters, 2005; 46: 4315–9.
- Gogoi P, Konwar D. An efficient and one-pot synthesis of imidazolines and benzimidazoles via anaerobic oxidation of carbon – nitrogen bonds in water. Tetrahedron letters, 2006; 47: 79–82.
- Dt N, Vsss GA, Mi R. Benzimidazole Derivatives as Potential Anxiolytics. J. Young Pharm; 2 (3):273–9.
- OECD guidelines for the testing of chemicals-Acute Oral Toxicity – Acute Toxic Class Method. 2001; (December):1–14.
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