It has been reported that expression

It has been reported that expression of murine haspin is found only in post-meiotic spermatids and that overexpression of murine haspin in HEK-293 cells leads to reduced cell proliferation. Therefore, it was suggested that haspin functions to bring about pkc pathway arrest in haploid germ cells (Tanaka et al., 1999). The data here confirm that human as well as murine haspin transcripts are most abundantly expressed in testis. However, all proliferating cell lines tested also expressed haspin mRNA, and haspin message was detected in thymus, bone marrow, fetal liver, and more weakly in spleen, intestine, lung and a variety of fetal tissues. Thus haspin expression correlates with tissues that have significant levels of cellular proliferation and differentiation. This, and the similarity in tissue distribution of human and murine haspin mRNA, suggests that haspin plays a physiological role in diploid as well as haploid cells and significantly broadens its likely functional relevance.
Acknowledgements
INTRODUCTION AND OBJECTIVES
METHODS
RESULTS
CONCLUSIONS
Introduction Several numbers of successful examples of pharmacophore hybridization strategies for drug design, discovery and development have been reported [1]. Hybridization concept was adopted to treat cancer and other multifactorial diseases in order to limit the use of chemotherapeutic agents, which are often limited because of the chemoresistance and/or undesirable toxic effects caused by the destruction of nonspecific cells at an effective dose of drugs. Isatin derivatives have been identified as natural scaffolds present in various traditional Chinese medicines with potent biological activity on different protein kinases [2] (Fig. 1). For example, isatin-based sunitinib maleate (Sutent®) was approved by the FDA for the treatment of advanced renal carcinoma and gastrointestinal stromal tumours. The hybrid anti-cancer agent, (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)- N8-hydroxyoctanediamide, with an isatin fragment based on kinase and histone deacetylase inhibitors, was also reported as an effective potential chemical probe for angiogenesis [3]. The main molecular mechanism of isatin derivatives is based on tyrosine kinase inhibition (TKIs) and inhibition of cyclin-dependent kinases (CDKs) by binding to the ATP pocket and/or caspase inhibition [4]. On the other hand, molecules bearing a rhodanine scaffold have been recognized as antineoplastic agents with a broad spectrum of activities against many cancer cell lines and several other biological activities [5] such as antidiabetic, antibacterial, antifungal, anticonvulsant, inflammatory and antiviral. The rhodanine derivatives are also known as inhibitors of many targets, such as HCV protease NS3 or NS5b [6] β-lactamase [7] UDP-N-acetylmuramate/l-alanine ligase, penicillin3 binding protein, histidine decarboxylase [8] cyclooxygenase, 5-lipoxygenase, cathepsin D, mannosyl transferase protein and JNK transferase [9]. They exhibit also submicromolar inhibitory activity against PDE4 [6], Jnk Stimulatory Phosphatase-1 (JSP-1) [10] and Plasmodium falciparum Enoyl acyl Carrier Protein Reductase (PfENR) [11] (Fig. 2). Despite this, only the rhodanine-based Epalrestat has been approved for the treatment of diabetic complications as aldose reductase inhibitor (Fig. 2) [12]. Although, some studies suggest that rhodanines are likely to be pan assay interference compounds (PAINS) due to their possible Michael acceptor functionality [13], experimental confirmations still essential and the positive aspect of such covalent modifiers was not be discarded as evidenced by numerous recent works reported in literature [14]. Recently, several isatin-rhodanine hybrids have been prepared and screened for their bioactivities. Some of them showed potent inhibitor activity against UDP-Galactopyranose Mutase UGM [15] (Fig. 3-Α), β-lactamase [16] (Infectious disease) (Fig. 3-B), and Histone acetyltransferases (wide range of diseases) [17] (Fig. 3-C).