ORIGINAL RESEARCH Triarylimidazoles-synthesis of 3-(4,5-diaryl-1H-imidazol-2-yl)-2- phenyl-1H-indole derivatives as potent a-glucosidase inhibitors Sadia Naureen • Shazia Noreen • Areesha Nazeer • Muhammad Ashraf • Umber Alam • Munawar Ali Munawar • Misbahul Ain Khan Received: 28 February 2014 / Accepted: 17 August 2014 Ó Springer Science+Business Media New York 2014 Abstract A series of new trisubstituted imidazoles-3- (4,5-diaryl-1H-imidazol-2-yl)-2-phenyl-1H-indole deriva- tives (2a–2u) were synthesized and evaluated for their a- glucosidase inhibition. The new compounds showed sig- nificant a-glucosidase inhibitory activity as compared to the standard inhibitor acrabose. Structures of synthesized compounds were determined using FT-IR, Mass spec- trometry, 1 H NMR, 13 C NMR, and elemental analyses. Keywords Multicomponent reactions  Benzil  Fisher indole synthesis  NMR spectra Introduction a-Glucosidases (EC 3.2.1.20) are intestinal enzymes responsible for the conversion of complex carbohydrates into simple sugars like glucose which is utilized as an energy source. a-Glucosidase inhibitors are used as anti- diabetic drugs for patients with type-2 diabetic mellitus. They retard the digestion of carbohydrates and hold up glucose absorption (Bonora and Muggeo, 2001). Imino- sugars, carbasugars, disaccharides, thiosugars, and non- sugar derivatives are among the various types of glucosi- dase inhibitors (de Melo et al., 2006). The ethanolamines, phenyl 6-deoxy-6-(morpholin-4-yl)-b-D-glucopyranoside (Fig. 1) (Balbaa M et al., 1999) have been also reported as glucosidase inhibitors. Acarbose (Fig. 2) (Schmidit et al., 1977), voglibose (Matsuo et al., 1992), and miglitol (Scott and Spencer, 2000) are commercial a-glucosidase inhibi- tors that are considered as first-line treatment for diabetic individuals with post-prandial hyperglycemia. The design of glucosidase inhibitors with a high degree of specificity and potency has attracted many research laboratories for the exploration of new inhibitors. Many agents in clinical use for treatment of diabeties, with dif- ferent mechanism of actions are e.g., Metformin (Bailey and Day, 2004) (Fig. 3), Rosiglitazone (Nissen and Wolski, 2007) (Fig. 4), Sulphonylurea (Geerley et al., 2010) (Fig. 5), and Chlorpropamide (Fitzgerald, 1962) (Fig. 6). Metformin and Rosiglitazone help to cause a decrease in insulin resistance, and Sulfonylurea and Chlorpropamide stimulate insulin release from pancreas. All these com- pounds seem to have a common feature –N–C–N– frag- ment represented by dotted lines. This ‘‘structural unit’’ seems to be intrinsically present in imidazoles. This made us interested in the chemistry of imidazoles carrying other heterocyclic rings and more especially in indole-based imidazoles and carry out their a-glucosidase inhibiting studies. The literature survey revealed that indole-based imid- azole compounds have versatile biological activities such as anti-cancer (Marchand et al., 2003), antibacterial (Pra- bhu and Radha, 2012), anti-inflammatory (Judy et al., 2011), and antifungal (Bhatnagar et al., 2011). Recently certain 4,5-diphenylimidazole-2-thione (Fig. 7), a quino- line (Fig. 8), and 4,5-diphenyl-1,2,4-triazoles-3-thiol (Balba et al., 2011) and imidazolines derivatives S. Naureen (&)  A. Nazeer  M. A. Munawar  M. A. Khan Institute of Chemistry, University of the Punjab, Quaid-i-Azam Campus, Lahore, Pakistan e-mail: phdline123@yahoo.com S. Noreen  M. A. Khan Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan M. Ashraf  U. Alam Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan 123 Med Chem Res DOI 10.1007/s00044-014-1239-y MEDICINAL CHEMISTR Y RESEARCH