A representation of the mechanism of action of the metal-organic trefoil knots.
PHOTO BY SUPPLIED
ABU DHABI – Researchers from New York University Abu Dhabi (NYUAD) have reportedly developed hybrid molecules that could serve as a new category of anti-cancer agents.
New findings about the molecules called metal-organic trefoil knots (M-TKs) are published in the journal Chemical Science.
“There is significant promise for developing new cancer therapies that can complement the existing chemotherapy options that are currently used to treat nearly half of all cancer patients undergoing chemotherapy,” said Ali Trabolsi, Associate Professor of Chemistry at NYUAD.
NYUAD research scientists Farah Benyettou and Thirumurugan Prakasam, led by Trabolsi, report that these nanoscale, water-soluble M-TKs showed high potency in tests against six cancer cell lines and live testing in zebrafish embryos.
The M-TKs were well tolerated by non-cancer cells but were significantly more potent than cisplatin, a common chemotherapy medication, in both human cancer cells–including those that were cisplatin-resistant–and in zebrafish embryos.
In cultured cells, M-TKs introduce reactive oxygen species (ROS) that damage the mitochondria of cancer cells, but not the nuclear DNA or the plasma membrane.
Benyettou said, “The researchers hypothesize that the molecules they have developed are less toxic to healthy cells because they are internalized less.”
In the next stage of developing M-TKs, research efforts will focus on the mechanism of action of the M-TKs to determine whether their ROS-mediated toxicity involves specific intracellular targets.
These findings confirm the viability of studying the effects of these compounds in whole vertebrates, as the M-TKs were well tolerated by zebrafish and appeared to selectively attack dividing cells.
Other NYUAD collaborators include fourth year graduate PhD student Tina Skorjanc, who contributed to the paper’s biological-related aspects.
The research was carried out using the Core Technology Platform resources at NYUAD, which are shared facilities that support research activities across disciplines.
This research is published in Chemical Science, the Royal Society of Chemistry’s flagship journal.
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