Development and Biological Evaluation of Imidazothiazole propenones as Tubulin Inhibitors that Effectively Triggered Apoptotic Cell Death in Alveolar Lung Cancer Cell Line

A new class of imidazothiazole‐propenones was synthesized and investigated for their anti‐proliferative activity against various human cancer cell lines. Promising activities were observed in five congeners 8 k, 8 l, 8 n, 8 o and 8 v with interesting cytotoxicity profiles. The detailed biological aspects of these congeners towards human lung cancer cell line (A549) were studied. Cell cycle assay revealed that these molecules arrested cell growth in G2/M phase of the cell cycle in a concentration‐dependent manner and lead to apoptotic cell death, confirmed by caspase‐3 activation assay. Further, the tubulin polymerization inhibition analysis results suggested that these congeners exhibited significant inhibitory effect on the tubulin assembly. Western blotting displayed that pro‐apoptotic proteins were markedly up regulated resulting in apoptosis. The investigations displayed that such congeners containing imidazothiazole‐propenone have the potential in the development of newer chemotherapeutic agents. A series of imidazothiazole‐propenone congeners were synthesized and evaluated for their anti proliferative activity. Five congeners 8k, 8 l, 8n, 8o and 8v showed significant anti proliferative efficacy on human lung cancer cells with an IC50 value of 0.4 to 1.04 μm. The immunochemistry assay revealed that these congeners exhibited significant inhibitory effect on the tubulin assembly leading to arrest of cell division (mitosis). Cell cycle assay revealed that these conjugates arrest cell growth at the G2/M phase and leads to apoptotic cell death which was confirmed by activation of Caspase 3 and up regulation of pro‐apoptotic proteins (p53, p21, cytochrome c and cyclin B1).