Chem SCI: discovery of a new anticancer drug

May 29, 2019 / biourn / - researchers from New York University and colleagues from the University's biological program have developed and studied the biological activities of five novel metal organic hybrid knot molecules, known as metal organic trefoil (m-tks) These molecules can effectively transfer metals to cancer cells, showing the potential as a new anticancer drug The study, published in chemical science, was led by chemistry professor Ali trabolsi and research scientist Farah benyettou and thirumurugan prakasam Trabolsi said that these nano scale, water-soluble m-tks showed high activity in six cancer cell lines in vitro and zebrafish embryos in vivo Photo source: Chemical Science m-tks is formed by self-assembly of a pair of single chelating ligands Are non cancer cells well tolerated in vitro, but the toxicity of cisplatin tolerant human cancer cells and zebrafish embryos is higher than that of cisplatin In the cultured cells, the introduction of ROS by m-tks can destroy the mitochondria of cancer cells, but not the nuclear DNA or cell membrane Trabolsi said: "the cytotoxicity and wide range of structural variation of m-tks indicate the potential of synthetic metal organic junctions as a new chemical field for drug design and development The development of new cancer therapy has a great prospect, which can supplement the existing chemotherapy scheme - the chemotherapy scheme used by nearly half of cancer patients when they receive chemotherapy at present "In many cases, the m-tks synthesized by thirumurugan prakasam has stronger anticancer activity than the previously reported cisplatin and other metal complexes The main delivery pathways of the drug are macropinocytosis and endocytosis mediated by caveolin and trellis, which are more active in cancer cells than in normal cells Cisplatin and other small molecules penetrate the cell through diffusion, so they have poor selectivity to tumor in vitro The researchers hypothesized that the molecules they developed were less toxic to healthy cells because they were less internalized In the next stage of m-tks development, the research will focus on the mechanism of m-tks to determine whether the ROS mediated toxicity involves specific intracellular targets These findings confirm the feasibility of studying the effects of these compounds on vertebrates as a whole, because zebrafish is well tolerated to m-tks and seems to be able to selectively attack mitotic cells Reference: Farah benyettou et al Potent and selective in vitro and in vivo antiproliferative effects of metal organic trefoil knots Chemical Science (2019) Doi: 10.1039/c9sc01218d