Design and Synthesis of a Modified RNA-Curcumin-demethylenated Piperoyl Conjugate as a Telomerase Targeted Antisense Prodrug; it's Activity against Human Cancer Cell Lines Hela & KB

摘要

The initiation and progression of cancer is controlled by both genetic and epigenetic events. The enzyme telomerase has a key role in controlling the lifespan of human cells. The notion that telomerase is reactivated in 80-90% of human cancers has led to the proposal of telomerase as a promising therapeutic target for novel anticancer inventions. Oligonucleotides (both deoxy and ribo) specially with modified backbone i.e. phosphorothioates have been extensively used in antisense therapeutics. Our observation that curcumin conjugate specially with piperic acid has multiple times enhanced bioavailability vis-a-vis curcumin against some bacteria and fungi and that curcumin is well reported as an antiproliferation agent, led us to combine the twin concepts i.e. antisense and prodrug for designing the molecule.