Anti-cancer activity of heteroaromatic acetals of andrographolide and its isomers.

Acetals ( 2a-d , 3a-d , and 6a-d ) of andrographolide ( 1 ), 14-deoxy-12-hydroxyandrographolide ( 4 ), and isoandrographolide ( 5 ) were synthesized using benzaldehyde and heteroaromatic aldehydes. All the synthesized derivatives were characterized using 1 H-NMR, 13 C-NMR, mass spectrometry, UV, and IR. The compound 6d was characterized via a single-crystal X-ray diffraction study. All the compounds were tested against 60 cell lines of NCI. The acetals ( 2a-d ) of andrographolide ( 1 ) exhibited better activity than the acetals ( 3a-d , and 6a-d ) of 12-hydroxyandrographolide ( 4 ) and isoandrographolide ( 5 ). Preliminary studies suggested that acetals synthesized using benzaldehyde improved anticancer activity. Compound 2a showed the highest growth inhibition of 90.97% against the leukaemia cancer cell line CCRF-CEM. Andrographolide and seven selected compounds were tested against the MDA-MB-231 breast cancer cell line. Compound 3b showed the best activity with an IC 50 value of 3 μM among all the tested compounds. Furthermore, this compound 3b was subjected to cell cycle analysis and protein expression confirming apoptosis through the disruption of the mitochondrial potential membrane (Δ ψ m ).