Products made from natural substances have been used and continue to be used to relieve numerous discomforts and health problems, and many of today’s medicines were developed from these types of substances, which were refined or synthesized to take advantage of all their benefits and minimize its possible toxic effects.
Now, natural compounds derived from the bark of the Brazilian lapacho tree have been used to create a therapeutic agent that could be effective in treating acute myeloid leukemia (AML), the most common type of acute leukemia in adults, which occurs due to an abnormal increase in the number of myeloid cells, a type of immature blood cell.
People affected by this type of cancer have a survival rate of around 20% after five years of diagnosis and their relapse rate is very high, hence “the importance of finding new therapeutic strategies for this disease”, has pointed out Gonçalo Bernardes, from the João Lobo Antunes Institute of Molecular Medicine (iMM) in Portugal, and professor at the University of Cambridge, in the United Kingdom), who has carried out research on this compound together with Gonzalo Jiménez-Osés, head of group from the Center for Cooperative Research in Biosciences, in Derio, Vizcaya.
Previously, the bark of another tree – the yew – had been used to develop a medical treatment, in this case taxanes to combat cancer, especially breast cancer. In their new study, which has been published in Nature Chemistry, these scientists describe the development of a new chemistry on natural compounds extracted from the bark of the Brazilian lapacho tree to produce an agent with therapeutic properties that would help treat acute myeloid leukemia.
Natural compound against leukemia without adverse effects
Both scientists have explained that there are many natural compounds with medicinal properties, but that currently it is not possible to use them as therapies because they are toxic and have adverse effects on healthy cells in the body. For this reason, in their study they have used previously modified natural compounds to mask the toxicity of some anticancer drugs until they reach their objectives, thus controlling their negative effects and taking advantage of their therapeutic potential. Previously, in 2018, they identified the target site of a compound from the bark of the lapacho tree that belongs to the orthoquinone family, called β-lapachone. These compounds are known for their potential to control the abnormal increase in the number of cells that causes cancer, and are good candidates for the treatment of leukemia.
“When the antibody meets the cancer cell, it binds to the CD33 marker and delivers the drug. At this point, it will convert to its active and toxic form, killing the cancer cell.”
Bernardes explained: “the compound that we explore in this study, called β-lapachone, is a promising drug to treat leukemia, but its reactive properties could have undesirable effects. In this work, we combine two strategies to minimize the negative effects of the compound. On the one hand, we add a chemical group to this compound that protects it from its reactive properties. It acts as a mask that covers the toxicity of the drug. This mask is released in a more acidic environment, which corresponds to the interior of the cells”. This activity gives way to a second strategy, in which, Jiménez-Osés continues, “the modified compound is attached to a protein, an antibody, which delivers it directly inside the cancer cells.”
Ana Guerreiro, co-author of the study adds that cancer cells have certain marks that distinguish them from healthy cells. In AML, specifically, one of these specific markers, CD33, is known to be found on neoplastic cells. “We bind our natural product to an antibody that specifically binds to this CD33. This allows the drug to pass through the body without harming any healthy cells, and when the antibody meets the cancer cell, it binds to the CD33 marker and delivers the drug. At this point, it will convert to its active, toxic form, killing the cancer cell.”
The results of the study are not only interesting as a new therapeutic approach for acute myeloid leukemia, but also the chemistry that these researchers have developed can be used with other natural compounds with therapeutic potential and whose medicinal use was not possible until now due to its toxic effects on healthy cells.
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