ASIAN JOURNAL OF CHEMISTRY ASIAN JOURNAL OF CHEMISTRY http://dx.doi.org/10.14233/ajchem.2014.17636 INTRODUCTION Cancer is a major public health concern worldwide. Transcending heart disease, cancer disease is the second leading cause of death due to different worldwide factors 1-4 . Cell division includes two following processes, mainly involves DNA copying and discrimination of replicated chromosomes into two separate cells. Initially, two stages are considered in cell division: mitosis (M), i.e. the process of nuclear split up and interphase i.e., the interval period between two M phases. The interphase stage constitutes G1, S and G2 phases through which the cells simply grow in size 5 . In the interphase stage, replication of DNA takes place in the S phase which is preceded by G1 phase; a gap during which the cell prepares for DNA synthesis. Another, gap called G2 come after G1, during which the cell gets ready for mitosis. G1, S, G2 and M phases are the main parts of the standard cell cycle. Before involvement in DNA replication, cells in G1 enter a resting state called G0. Cells in G0 account for the major part of the non-growing, non-proliferating cells in the human body. In cancer, cell proliferation results mainly from alterations in the genetic control of cell division. Two classes of genes are involved in this mutation including protooncogenes and tumour suppressor genes. In normal cells, the products of Synthesis and Characterization of bis-3,5-Disubstituted Thiadiazine-2-thione Derivatives as Anticancer Agents A.A. RADWAN 1,2,* , T. ABOUL-FADL 3 , A. AL-DHFYAN 4,5 and W.M. ABDEL-MAGEEDA 6,7 1 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt 2 Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia 3 Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt 4 Stem Cell Therapy Program, King Faisal Specialized Hospital and Research Center, Riyadh 11211, Saudi Arabia 5 Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia 6 Pharmacognosy Department, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia 7 Pharmacognosy Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt *Corresponding author: Tel: +966 146 70562; E-mail: dhna_2001@hotmail.com Received: 20 March 2014; Accepted: 21 May 2014; Published online: 15 November 2014; AJC-16313 Selective cytotoxic effect toward tumor cells but not the normal tissues represent a major challenge in cancer drug discovery. Herein, we describe the synthesis and selective antitumor activity of some HHT. All the synthesized compounds showed a good antitumor activity against leukemia K562 cells. In regard to cytotoxicity in normal cells, compounds (1-11) showed no cytotoxic effect within 200 μM range, however compounds 12-16 showed non-selective cytotoxic effect. Keywords: Synthesis, Thiadiazine-2-thiones, Anticancer. protooncogenes act at different levels along the pathways that stimulate cell proliferation 6 . Virus and inherited predisposing factors that contribute to mutated versions of protooncogenes or oncogenes can impair the G1 checkpoint function and promote tumour growth. During cytotoxic cancer treatment, more than half of all human cancer cells with impaired G1 function rely on the G2 to outrun the DNA damage. In normal cells, the G2 cell cycle is rarely utilized, which makes G2 checkpoint abrogation strategy attractive in cancer treatment 7,8 . Vinca alkaloids and taxanes are clinically used chemothera- peutics to control some types of cancer through their notable suppression of G2/M transition. The complex chemical- structures of these compounds limit the possible structural modification and subsequently restrict the optimization of its anticancer activity. Thus, modulators of the G2/M checkpoint that have small molecular structures are of particular interest chemotherapeutic agents 9 . Through our data from studies on the tetrahydro-(2H)- 1,3,5-thiadiazine-2-thione (THTT) nucleus displays different biological activities 6,10-16 including antitubercular, antibacterial, antiviral, antifungal, anthelmenthic and anticancer activities. The biological activity of these compounds was suggested based on isothiocyanates and dithiocarbamic acid species that are liberated in the biosystem upon hydrolysis 17,18 . Furthermore, Asian Journal of Chemistry; Vol. 26, No. 23 (2014), 8145-8150