Cytotoxic Activity and Apoptosis-Inducing Potential of Di-spiropyrrolidino and Di-spiropyrrolizidino Oxindole Andrographolide Derivatives

• DOI: 10.1371/journal.pone.0058055
• Publication Date: 2013-03-05T22:34:41Z
• Authors: Sumit Kumar Dey; Dipayan Bose; Abhijit Hazra; Subhendu Naskar; Abhishek Nandy; Rudra Narayan Munda; Subhadip Das; Nabanita Chatterjee; Nirup Bikash Mondal; Sukdeb Banerjee; Krishna Das Saha
• Keywords: Andrographolide; HeLa; Oxindole

Anticancer role of andrographolide is well documented. To find novel potent derivatives with improved cytotoxicity than on cancer cells, two series di-spiropyrrolidino- and di-spiropyrrolizidino oxindole prepared by cyclo-addition azomethine ylide along sarcosine or proline (viz. respectively) substitution different functional groups (-CH3, -OCH3 halogens) were examined for their cytotoxic effect a panel six human cell lines (colorectal carcinoma HCT116 pancreatic MiaPaCa-2 hepatocarcinoma HepG2 cervical HeLa lung A549 melanoma A375 cells). Except halogen substituted CY2, CY14 CY15 Br, Cl I respectively), none the other showed in examined. Order compounds CY2>CY14>CY15>andrographolide. Higher toxicity was observed HCT116, cells. induced death (GI50 10.5), 11.2) 16.6) cells associated rounding, nuclear fragmentation increased percentage apoptotic cycle arrest at G1 phase, ROS generation, involvement mitochondrial pathway. Upregulation Bax, Bad, p53, caspases-3,-9 cleaved PARP; downregulation Bcl-2, cytosolic NF-κB p65, PI3K p-Akt; translocation P53/P21, p65 seen CY2 treated Thus, three halogenated are found to be more some The most derivative, involves dependent pathway like andrographolide.