[ad_1]
Aspirate bone marrow with acute myeloid leukemia. Several explosions have Auer canes. Credit: Wikipedia
Researchers in chemistry at Oregon State University have patented a method of making anti-leukemic compounds, which was until now only available via an Asian tree that produces them.
The synthesis of cephalotaxine and homoharringtonine (HHT) paves the way for cheaper and more readily available leukemia drugs, the production of which is not subject to risk and ineffectiveness badociated with the harvesting of natural sources.
In addition, synthesis of cephalotaxin paves the way for the preparation of other structurally related compounds for evaluation as potential new cancer drugs.
"We want to work in partnership with the industry so we do not have to grow trees to get that," said author Christopher Beaudry, badociate professor of chemistry at the Faculty of Science. from the OSU. "And maybe we could find a more potent inhibitor of protein translation, or a more selective inhibitor." This molecule could also find an application to block the synthesis of bacterial proteins, which would be useful for treating resistant pathogens to antibiotics. "
The results were published in Angewandte Chemie.
HHT, also known as Synribo or omacetaxine mepesuccinate, is used to treat chronic myeloid leukemia, one of the four main types of the disease.
Historically, HHT has been made by adding an ester to cephalotaxine, an alkaloid derived from the leaves of an Asian tree: plum yew. And the only way to get more cephalotaxin was to plant more prune yews.
This is problematic, Beaudry said.
"The trees do not grow very fast," he said. "And any kind of agricultural problem can affect the production of the material.Using chemical synthesis, we can start with basic chemicals to make cephalotaxin, and we will further optimize the process to make it commercially viable."
Leukemia is a type of cancer that originates in the hematopoietic cells of the bone marrow. In the United States, nearly 200,000 people are diagnosed with leukemia each year.
Myeloid leukemias, also called myelocytic or myeloid leukemia, start in early myeloid cells. Myeloid cells are ultimately transformed into platelet-producing cells and white blood cells other than lymphocytes.
Chronic myelogenous leukemia develops slowly and most patients can live with it for several years, but it is harder to cure than the acute form of the disease. It is characterized by a chromosomal abnormality that leads to an overproduction of proteins, leading to the proliferation of cancer cells.
Chronic myeloid leukemia is treated with drugs, such as Gleevec, that bind to a carcinogenic protein and inactivate it – until the cancer is molted and the drug no longer works, that is. is where HHT comes in. HHT stops producing all the proteins that fast-growing leukemic cells need.
In addition, HHT is promising to counter stem cells of chronic myeloid leukemia, as well as to fight against other cancer cell lines.
Beaudry and graduate student Xuan Ju used an oxidative cycle opening of a furan, a type of organic compound, to trigger HHT synthesis via a reaction known as spontaneous Mannich transannular cyclization.
"From start to finish, at nine stages of the chemical we buy, the yield is greater than 5%, which may sound awful, but actually very good," Beaudry said. "As a rule of thumb, the performance of any process would be much lower – think about the amount of tree mbad needed to make VHT – and we think we can also make other improvements."
Explore further:
New combination therapy targets pre-leukemic stem cells
More information:
Xuan Ju et al, total synthesis of (-) – cephalotaxine and (-) – homoharringtonine by Furan-Transannular Mannich oxidation cyclization, Angewandte Chemie International Edition (2019). DOI: 10.1002 / anie.201902174
Source link
