High Throughput Screening of Focused Virtual Library and Synthetic Protocols of Marine Sponge Derived Hymenialdisine Analogs as Potential Abnormal Signal Transduction Inhibitors

Abstract

Cellular proliferation is the process of mitotic cell division by which a cell grows, replicates its DNA and divides to produce two daughter cells. Mitotic cycle is regulated by cyclin-dependent kinases (CDKs) and tyrosine proteine kinases (TPKs). CDKs are binary proline-directed serine-threonine-specific protein kinases consisting of a positive regulatory subunit known as cyclin. The role of the CDKs is to control cell cycle progression through phosphorylation of proteins that function at specific cell cycle stages [1]. Tyrosine kinase catalyzes phosphorylation of tyrosine residues in proteins. The phosphorylation of kinase residue results in many signal transduction cascades wherein extracellular signal is being transmitted by cell membrane receptors such as EGFr/FGFr/PDGFr/C-src. Extra cellular signal enters into the nucleus to cause genetic mutation which further leads to the progression of cancer [2]. CDKs and TPKs can regulate the checkpoints. Their control mechanism ensures that everything is ready for DNA synthesis and mitosis phase division; thereafter complete cell division. Dispute of the checkpoints may lead to abnormal signal transmission that may produce oncogenic cell signaling and cancer. Abnormal signal transduction may be produced by the different mutagens such as virus, bacteria and chemical [1].