Aboul-Enein and El Rashedy. Med chem 2015, 5:7 DOI: 10.4172/2161-0444.1000280 Review Article Open Access Med chem ISSN: 2161-0444 Med chem, an open access journal Volume 5(7): 318-325 (2015) - 318 Benzimidazole Derivatives as Antidiabetic Agents Hassan Y Aboul-Enein 1 * and Ahemd A El Rashedy 2 1 Pharmaceutical and Medicinal Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Cairo 12311, Egypt 2 Natural and Microbial Department, National Research Centre, Dokki, Giza 12622, Egypt *Corresponding author: Hassan Y. Aboul-Enein, Pharmaceutical and Medicinal Chemistry Department, National Research Centre, Dokki, Cairo 12311, Egypt, Tel: +201003678948; Fax: +20233370931; E-mail: haboulenein@yahoo.com Received June 01, 2015; Accepted July 17, 2015; Published July 25, 2015 Citation: Aboul-Enein HY, El Rashedy AA (2015) Benzimidazole Derivatives as Antidiabetic Agents. Med chem 5: 318-325. doi: 10.4172/2161-0444.1000280 Copyright: © 2015 Aboul-Enein HY, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: Benzimidazole derivatives; Antidiabetic agents; Pharmacological activity; Mechanism of action; Synthesis Diabetes mellitus (DM) is a chronic metabolic disease which result due to no production of insulin causing type 1 DM or due to partial and/or insufcient production of insulin causing type 2 DM. Furthermore , insulin resistance cause hyperglycemia and diabetes due to the inability of the cells to use insulin properly and efciently. Some to the serious complication of diabetes include nephropathy, retinopathy, neuropathy, foot ulcers among other symptoms [1]. One of the most widely used antidiabetic agents are the sulfonylureas which act through the stimulation of the pancreatic β-cells for the secretion of insulin. Another class of antidiabetic agents are thiazolidinediones e.g. glibenclamide, ciglitazone and troglitazone. Tese drugs stimulate insulin secretion and therefore are efective in treatment of in a type-2 diabetic patients. Metformin which belongs to the biguanides group which enhance insulin action at the post receptor level in peripheral tissues such as muscle [2]. “Shingalapur et al. [3] synthesized a series of 1,3,4-oxadiazoles derivatives containing 2-mercapto benzimidazole moiety and screened for in vivo antidiabetic activity using oral glucose tolerance test (OGTT)”. Some of these derivatives showed improved reduction in blood–glucose levels compared with glibenclamide (Scheme 1). N H N S O N N R 1 1 R= 4-OH,2-OH,Fufurayl, naphthalen-2-ol Some new benzimidazole containing thiazolidinone 2, 3 were also reported for anti-diabetic activity. Both compounds were found to be more potent in hyperglycemic and normoglycemic models at a dose of 50 mg/kg [4]. N H N N S H3CO O COOH N H N N S H3CO O 2 3 A series of bis-benzimidazole derivatives were synthesized and found that compound 4 has showed signifcant antidiabetic activity when compared to glibenclamide as standard drug [5] (Scheme 2). N H N (CH 2 )n H 3 C N N H CH 3 n=2, 3,6 ,7 4 Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and insulin sensitivity [6,7]. Insulin resistance by itself will not result in T2DM unless β-cell secretion of insulin is decreased. Based on the Centers for Disease Control and Prevention National Diabetes Fact Sheet in 2007 [8], there were 23.6 million Americans with diabetes, of whom 90% to 95% have T2DM. Peroxisome Proliferator Activated Receptors (PPARs) act as regulators of lipid and glucose metabolism. Tis resulted in the development of synthetic drugs which represent a potential tool for Abstract Benzimidazole is an important pharmacophore which was included in several biologically active compounds resulted in the development of several classes of drugs. This review discusses the synthesis of benzimidazole derivatives as a target agents for antidiabetic by different mechanism such as peroxisome proliferator – activated receptor α transcriptional activity, glycosidases receptor, dipeptidyl peptidase IV, glucokinase, human glucagon receptor (hGCGR) antagonist , aldose reductase enzyme and stearoyl- CoA desaturase . NH 2 NH 2 N H N SH + ClCH 2 COOC 2 H 5 a b N H N SCH 2 COOC 2 H 5 d N H N SCH 2 N N O Ar Scheme 1: Reagent and condition: (a) CS 2 , NaOH, EtOH; (b) EtOH (c) EtOH, NH 2 NH 2 .H 2 O (d) Ar -COOH , POCl 3 Scheme 2: Benzimidazole as Peroxisome proliferator N H N (CH2)n H3C N N H CH3 NH2 NH2 + COOH (CH2)n COOH 70-90 C ,20hr phosphotungstic acid(PTA) M e d i c i n a l c h e m i s t r y ISSN: 2161-0444 Medicinal chemistry