Month 2018 Synthesis, Characterization, and Anticancer Activity (MCF-7) of Some Acetanilide-based Heterocycles Ehab Abdel-Latif,* Eman M. Keshk, Abdel-Galil M. Khalil, Ali Saeed, and Heba M. Metwally Department of Chemistry, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt *E-mail: ehabattia00@gmx.net Received April 8, 2018 DOI 10.1002/jhet.3294 Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com). A series of some novel 4-(N-substituted amino)-acetanilide scaffolds was synthesized through the nucleophilic substitution reactions of the highly versatile N-(4-acetamidophenyl)-2-chloroacetamide (3) with various types of nucleophilic reagents such as benzothiazole-2-thiol, ethyl 2-mercaptoacetate, 4,6-dimethyl- 2-mercapto-nicotinonitrile, various thiocarbamoyl derivatives, ammonium thiocyanate, 3-cyano-4,6- dimethyl-5-arylazopyridin-2-ones, and malononitrile. The synthesized 4-(N-substituted amino) acetanilide scaffolds were characterized by spectral analyses and assayed in vitro for breast anticancer activity. 2-(4- Acetamidophenylaminocarbonyl)-3-amino-thiophenes 11, 13a, and 13b showed the highest cytotoxic activity. J. Heterocyclic Chem., 00, 00 (2018). INTRODUCTION Since the discovery of acetanilide as analgesic under the name of Antifebrin [1], acetanilide derivatives have gained much attention in medicinal chemistry. Literature studies expose that acetanilide derivatives are an important structural backbone of biologically active molecules. They showed various activities such as antimicrobial [2,3], antiviral [4,5], anthelmintic [6], anti-inflammatory [7], cytotoxic [8,9], antifungal, and antibacterial [10,11]. Moreover, they possess anti-arthritic [12], analgesic [13], antileishmanial [14], antitumor [15], and insecticidal [16] properties. Away from the famous activity of acetanilides, literature studies reveal a potent anticancer activity for those compounds. For example, AZD1152 [17] (Fig. 1) inhibited cell division and cell proliferation in Aurora kinase B overexpressed tumor cells. 2-[Benzimidazole-2- yl)sulfanyl]-N-[4-(2-methylthiazol-4-yl)phenyl]acetamide compounds [18] (Fig. 1) were found to have a potent effect against A549 and C6 tumor cell lines. Histone deacetylase inhibitors (HDACi) such as suberoylanilide hydroxamic acid [19,20] (Fig. 1) has shown potent cytotoxic effects against several tumor types with low toxicity towards normal cells. Chloroacetamides are valuable synthetic intermediates as they allow the incorporation of unmined heteroatoms to afford a wide range of heterocycles. In this paper, we describe the synthesis and anticancer activity of many acetanilides incorporating thiophene, thiazole, pyridine, and/or pyrrole moieties through different linkages. RESULTS AND DISCUSSION Chemistry. The starting scaffold N-(4-acetamidophenyl)- 2-chloroacetamide (3) has been prepared by the reported experimental conditions through treatment of © 2018 Wiley Periodicals, Inc.