Synthesis, docking and in vitro anticancer evaluation of some new benzopyrone derivatives Sohair L. El-Ansary a,b , Mohammed M. Hussein a,b , Doaa E. Abdel Rahman a,⇑ , Lina M.A. Abdel Ghany b a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt b Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Misr University for Science and Technology, 6th October City, Egypt article info Article history: Received 20 October 2013 Available online 19 February 2014 Keywords: Benzopyrones Anticancer Docking studies Casein kinase II abstract The synthesis of some new 3-alkyl-7-hydroxy-4-methyl-8-substituted-1H-benzopyran-2-ones, 6-alkyl-7-methyl-2-substituted amino-5H-pyrano[6,5-e] benzoxazol-5-ones, 7-alkyl-8-methyl-3-substi- tuted-2,6-dihydropyrano[6,5-f]-1,4-benzoxazin-6-ones, 7,8-disubstituted-3-ethyl-4-methyl-1H-benzo- pyran-2-ones and 3-alkyl-4-methyl-7-substituted-1H-benzopyran-2-ones were described. Fourteen compounds were selected by National Cancer Institute (NCI), Bethesda, and evaluated for their in vitro anticancer activity in the full NCI 60 cell lines panel assay by a single dose test. Compounds 4a, 18a, 18b and 23a were found to be broad-spectrum antitumors showing effectiveness toward numerous cell lines that belong to different tumor subpanels. Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the binding site of the casein kinase II (CK2) enzyme which is involved in cell survival and proliferation through a number of downstream effectors. Ó 2014 Elsevier Inc. All rights reserved. 1. Introduction Cancer is a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in 2008 and deaths from cancer worldwide are projected to continue to rise to over 13.1 million in 2030 [1]. Cancer cells develop a degree of autonomy and grow uncontrollably disregarding the normal rules of cell division, resulting in uncontrolled growth and proliferation. In fact, almost 90% of cancer- related deaths are due to tumor spreading or dissemination [2]. Several techniques involving surgery, radiation, immunotherapy and chemotherapy were adopted for eradication of cancerous cells. Unfortunately, no currently available anticancer drugs would eradicate cancer cells without harming normal tissues [3]. Accordingly, continued research is needed to develop new and efficient antitumor agents. Benzopyran-2-one comprises a group of natural compounds found in a variety of plant sources. Benzopyran-2-ones are recog- nized to possess a wide variety of biological activities against bac- teria [4,5], fungi [6] and protozoa [7]. In addition, they are also reported to possess anti-inflammatory [8], antioxidant [6,9], antiallergic [10], antithrombotic [11], antiHIV [12], antidepressant [13–15], photosensitizing [16,17], estrogenic like [18] and antican- cer activities [19–22]. Warfarin A (Fig. 1) reduced metastases from intestinal carcinomas to a great extent [23] and also used as an ad- junct to the surgical treatment of malignant tumors [24]. The inhibition activity of benzopyran-2-one derivative B (Fig. 1) against different cancer cell lines showed a high selectivity for HU- VEC that can be potentially utilized as lead compound to develop non toxic angiogenesis inhibitors and small molecular ligands to target HUVEC [25]. In addition, daphnetin C (Fig. 1) was proven to act as tyrosine kinase inhibitor. Daphnetin inhibited tyrosine kinase, epidermal growth factor receptor, serine/threonine- specific protein kinase, and protein kinase C in vitro [26]. Also, benzopyran-2-one deriva- tive D (Fig. 1) was identified as a novel class of MEK 1 kinase inhib- itors [27]. Furthermore, some heterocycles such as oxathiazolidine [28], triazole [29], oxazole [30] and thiadiazole [31] were found to pos- sess potential antitumor activity. These findings have encouraged us to prepare compounds con- taining the benzopyran-2-one nucleus substituted at 7-position with different bioisosteric moieties as triazole, thiadiazole, thiazo- lidinone, thiazole, hydrazone, oxathiazolidine, dihydropyrazole, dihydropyrrole and dioxopyrrolidine. Also, 8-substituted deriva- tives as chalcones, dihydropyridines, ureas and imidazolidinetri- ones in addition to oxazolo and oxazinobenzopyran-2-one derivatives were prepared. Fourteen compounds of the synthesized compounds were selected by National Cancer Institute (NCI), http://dx.doi.org/10.1016/j.bioorg.2014.02.003 0045-2068/Ó 2014 Elsevier Inc. All rights reserved. ⇑ Corresponding author. E-mail addresses: doaaezzat2004@yahoo.com, doaaezzat2004@cu.edu.eg (D.E. Abdel Rahman). Bioorganic Chemistry 53 (2014) 50–66 Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg