Design and Synthesis of Benzothiazole Derivatives Having Potential Targeted Anticancer Activity

Abstract

Cancer is a disease in which a group of abnormal cells grow uncontrollably by disregarding the normal rules of cell division. Normal cells are constantly subjects to signals that dictate weather the cell should divide and differentiate to another cell or die. Apoptosis is a normal physiological process which is very crucial to maintain tissue homeostasis. Dysregulated apoptosis can lead to various diseases as cancer. Thus, evasion of apoptosis stands out as a key hallmark of cancer cells. BCL-2 family of proteins is the key modulator of the mitochondrial apoptotic pathway. Therefore, the balance between the anti-apoptotic (BCL-2, BCL-XL and MCL-1) and pro-apoptotic (BAK, BAX, BAD, PUMA and NOXA) members of this family will govern cell fate. Overexpression of anti-apoptotic BCL-2 members is implicated in the progression of many human cancers as well as the emerging resistance to various anti-cancer agents including targeted therapies. Indeed, inhibition of the anti-apoptotic BCL-2 members by small molecule BH3 mimetics may provide an excellent approach in cancer therapy.