Novel shield against toxic haem
doi:10.1038/nindia.2011.81 Published online 14 June 2011
Researchers have synthesized a type of novel alkaloid that could protect against the toxic effects of free haem, an essential molecule usually bound to haemoglobin and other proteins. These alkaloids could be effective for treating haem-induced toxicity, which wreaks havoc on vital organs such as kidneys and the heart.
Haem is an important molecule that has roles in drug detoxification, oxygen transport and respiration in living organisms. Haemoglobin releases free haem during various pathological stages, through a process that generates reactive oxygen species. Such reactive oxygen species can cause damage to lipids, proteins and even DNA and vital biological cells. So far, however, no antidote has yet been capable of counteracting this toxicity.
To devise an effective antidote, the researchers turned their attention to natural products. Previous studies have shown that acridone, a type of alkaloid found in the root bark of citrus fruits, exhibits anticancer, antiviral and antiparasitic properties. Taking cues from this, the researchers successfully synthesized acridone and its novel derivatives such as arborinine. They then studied the efficacy of arborinine and other acridone derivatives for fighting the toxic effects of free haem.
The alkaloids showed an affinity to bind to haem, which is essential for thwarting its toxic effects. The study found that arborinine and other acridone derivatives were able to prevent the haem-induced degradation of bovine serum albumin, a protein molecule.
"At this stage, it is too early to class these molecules as potential drug candidates," says lead researcher Susanta Sekhar Adhikari. Because these molecules protect proteins from haem-induced toxicity, they could have important roles in haem-induced pathology, he adds.
- Pal, C. et al. Synthesis of novel heme-interacting acridone derivatives to prevent free heme-mediated protein oxidation and degradation. Bioorg. Med. Chem. Lett. 21, 3563-3567 (2011)