Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2017, 9(9):210-219 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 210 Synthesis and Biological Evaluation of Imidazopyrmidine-Propenone Conjugates as Potent Tubulin Polymerization Inhibitors MVPS Vishnuvardhan, Ibrahim Bin Sayeed, V Lakshma Nayak, Mohd Adil Shareef and Ahmed Kamal * Medicinal Chemistry and Biotechnology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad, India _____________________________________________________________________________ ABSTRACT A library of imidazopyrimidine-propenone conjugates (8a-8g) were synthesized and evaluated for their antitumor activity against three human cancer cell lines namely prostate (DU-145), lung (A549) and breast (MCF-7) cancer. These conjugates showed good to moderate activity against the tested cell lines. Among them two conjugates (8c and 8d) showed significant antiproliferative activity against human lung cancer cell line (A549) with an IC50 values of 1.236 μM and 1.327 μM respectively. Flow cytometric analysis revealed that these conjugates 8c and 8d arrest the cell cycle at the G2/M phase and induce cell death by apoptosis. The tubulin polymerization assay showed that these compounds 8c and 8d effectively inhibited the microtubule assembly in human lung cancer cells (A549). The molecular modeling studies showed that the compound 8c interacts and binds efficiently with the tubulin protein at the colchicine site. Overall, the present investigation demonstrated that the synthesized imidazopyrmidine- propenone conjugates are promising tubulin inhibitors. Keywords: Imidazopyrimidine-propenone; Anticancer activity; Tubulin polymerization; Molecular modeling _____________________________________________________________________________ INTRODUCTION Cancer is a dreadful disease marked by uncontrolled proliferation of abnormal cells which invades to other organs of body leading to morbidity and mortality. Cancer is one of the leading causes of death around the globe where nearly 8.5 million people die of cancer in 2015. Mi crotubule is a heterodimeric protein made of two sub units that is α- tubulin and β-tubulin. They are long, filamentous, tube shaped protein polymers that are essential in all eukaryotic cells. Microtubule perform various funtions in cell such as development and maintenance of cell shape, cell signalling, transport of vesicles and other components throughout the cells apart from cell division (mitosis) [1,2]. Microtubules plays a prominent role in building up of mitotic spindle during mitosis which makes them an promising target for anticancer drugs. Microtubules and their dynamics with multiple tubulin-binding sites are the targets of a chemically diverse group of antimitotic drugs that have been used with great success in the treatment of cancer. Here are some of the microtubule targeting agents shown in (Figure 1). Imidazopyrimidine is a fused bicyclic heterocylce with three nitrogen that represent an important class of privileged scaffold [3-6]. imidazopyrimidine scaffold displays a broad profile of biological activity, tumour suppression being important among them [7]. Many attempts to discover new drugs with novel technologies have fallen short of producing the desired results. Henceforth, privileged structure guided scaffold re- modification is one of the primary strategy to identify structurally new chemo types by modifying either the central core of the scaffold or by modifying the side- chain of existing active compounds [8]. Thus imidazopyrimidine scafflod provide an immense scope to utilize undescribed bioactivities by making use of existing motifs with well established synthetic protocols of imidazopyrimidine.