Synthesis and biological evaluation of andrographolide analogues as anti-cancer agents

• C14-ester analogues of andrographolide (AG) and their epoxy derivatives were prepared.
• Analogues were screened against kidney (HEK-293) and breast cancer (MCF-7) cells.
• Three analogues were more cytotoxic than AG and non-cytotoxic toward normal cells.
• Apoptosis was checked by caspase 3 staining, FACS, western blotting, NF-κB activity.

A new family of andrographolide analogues were synthesized and screened in vitro against kidney (HEK-293) and breast (MCF-7) cancer cells. The anti-cancer effects of the active analogues (2b, 2c and 4c) were determined by multiple cell based assays such as MTT, immunostaining, FACS, western blotting and transcriptional inhibition of NF-κB activity. Importantly, these compounds were found to possess higher anti-cancer potency than andrographolide and low toxicity to normal (VERO and MCF-10A) cells. Increased level of Bax/Bcl-xL ratio, caspase 3, and sub G1 population, higher expression level of tumor suppressor protein p53 and lower expression level of NF-κB suggested potent apoptotic property of the active analogues. Data revealed that the andrographolide derivative-mediated cell death in cancer cells was p53 dependent.

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