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Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structure-activity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 μM against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlich's ascitic and solid Sarcoma-180 mouse models.

Background: Genotoxic effects of many of clinically useful anticancer drugs are due to their interaction with the amino groups of nucleic acids. Literature reveals that the chalcones however may be devoid of this important side effect. With this view in mind, we synthesized a novel quinazolinone-chalcone derivative and evaluated its anticancer potential. Methods:Anticancer potential of A novel quinazolinone-chalcone derivative 2- 4, was determined through MTT assay, colony formation assay, Wound healing assay, Cell cycle and Western Blot Analysis in Mia paca-2 cells treated with 8b. Results:The cytotoxicity studies showed a concentration dependent decrease in cell viability of HCT-116, HL-60, PC-3, A-549, Mia pacca-2 and MCF-7 cell lines with IC 50 values ranging from 5.5 to 8.5 µM. The motility of Mia paca-2 cells treated with 8b was found inhibited in a dose dependent manner. Cell cycle studies revealed a concentration dependent rise in G2/M phase of cell cycle from 1% to 52%. Decreased expression of cyclins regulating G2/M transition of the cell cycle (cyclin B1 and cdk1) was recorded after treatment of Mia Paca-2 cells with 8b. Mitochondrial membrane potential was also significantly lost in cultures exposed to 8b. However, nuclear morphology of 8b treated Mia paca-2 cells revealed no significant changes. 8b significantly inhibited the growth of Ehrlich ascites carcinoma, Sarcoma-180 (ascites), Ehrlich tumor (solid) and Sarcoma-180 (solid). Conclusion:The findings are indicative of 8b exerting anticancer activity through cell cycle arrest at G2/M phase and not through apoptosis. Reduction in the motility of Mia paca-2 cells indicates anti-metastatic potential of 8b.