Short communication Synthesis of benzimidazoles bearing oxadiazole nucleus as anticancer agents Mohd Rashid, Asif Husain * , Ravinesh Mishra Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India highlights graphical abstract < 25 Novel benzimidazoles bearing oxadiazole nucleus were synthe- sized under microwave irradiation. < Initial screening of compounds showed significant to good in vitro anticancer activity. < One compound, 1beA 18 , emerged as lead compound and screened at five dose level. < The compound 1beA 18 can be used as a template for designing potential anticancer agents. article info Article history: Received 16 November 2011 Received in revised form 15 April 2012 Accepted 18 April 2012 Available online 9 May 2012 Keywords: Benzimidazole 1,3,4-oxadiazole Microwave-assisted Anticancer activity abstract Starting from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (1), twenty new 1-(1H-benzo[d] imidazol-2-yl)-3-(1,3,4-oxadiazol-5-substituted derivatives-2-yl)propan-1-ones (1beA 7e26 ) were synthesized under microwave irradiation in good yields. Further, compound 1beA 7 was reacted with different secondary amines under microwave irradiation to produce five novel 1-(1H-benzo[d]imidazol- 2-yl)-3-(5-(methyl substituted)-1,3,4-oxadiazol-2-yl)propan-1-ones (1beA 7aee ). The title compounds were screened for their in vitro anticancer activity at National Cancer Institute (NCI), USA; at a single dose (10 mM) in NCI 60 cell line panel and results showed significant to good anticancer activity. One compound, 1beA 18 (NSC: 759205), 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(2,4-dichlorophenyl)-1,3,4- oxadiazol-2-yl)propan-1-one, emerged as lead compound; it was selected for five-dose level screening and found to have significant growth inhibition activity. Ó 2012 Elsevier Masson SAS. All rights reserved. 1. Introduction Cancer is a collection of different life threatening diseases characterized by uncontrolled growth of cells, leading to invasion of surrounding tissue and often spreading to other parts of the body. When it comes to understanding and controlling cancer, scientists are now working from a position of strength e a sturdy foundation of knowledge about cancer built over the past 50 years. There is an urgent need for novel effective drug regimens for the treatment of cancer because the current chemotherapy suffers from a slim therapeutic index, with significant toxicity from effective drug doses or tumor recurrence at low drug doses. Searching of new anticancer agents having heterocyclic nucleus continues world- wide at various laboratories [1e3]. Scientists from worldwide have reported remarkable antitumor/ antiproliferative/anticancer [4e13], anti-inflammatory [12], anti- viral including anti-HIV [13,14], antibacterial [15e17], antifungal [18,19] and antioxidant [19,20] activities of different benzimidazole derivatives. Similarly, 1,3,4-oxadiazole is a class of heterocyclic compound that have attracted significant interest in medicinal chemistry as they have a wide range of pharmaceutical and phar- macological applications including potential antitumor, anti- proliferative or anticancer activities [21e26]. Benzimidazole clubbed with other heterocyclic moieties including the oxadiazole * Corresponding author. Tel.: þ91 11 26059681/688x5890; fax: þ91 11 16988874; þ91 9891116086 (mobile). E-mail address: drasifhusain@yahoo.com (A. Husain). Contents lists available at SciVerse ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech 0223-5234/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmech.2012.04.027 European Journal of Medicinal Chemistry 54 (2012) 855e866