Novel Compounds May Lessen Chemotherapy-Induced Adverse Events


Compounds demonstrate high cancer-killing activity and low-toxicity in non-tumor cell line.

New compounds demonstrate potent anticancer activity in breast and colon tumor cell lines, which could decrease adverse events (AEs) during chemotherapy.

For the study, investigators designed a series of small molecules or bonds that downregulate the expression of various genes by joining the G-quadruplex, causing inhibitory effects on cell growth.

The novel compounds contain parts of sugar in their chemical structure to facilitate the entry into cancer cells, reach the chromosomes, and prevent telomerase to confer immortality to these cells.

“These compounds act against telomeres, structures of the chromosomes that are shortened in each cell division,” said investigator Eva Falomir. “When the shortening is very prolonged, the cell ages and dies. This is natural, but in cancer cells shortening does not occur because an enzyme, telomerase, prevents the shortening of telomeres: tumor cells do not age and become immortal, so it is so difficult to fight them.”

The work is part of the new therapeutic strategies in oncology that boycotts the mechanisms that allow uncontrolled tumor cell proliferation.

“Before, antitumor treatments were very unspecific and caused [AEs] in other parts of the body not affected by the tumor,” said Miguel Carda Usó. “Treatments that are more specific are now being sought for each type of cancer, and these new compounds should be applied to personalized therapies that would lessen the [AEs} of oncological treatments.”

These compounds may lead to the development of cancer drugs with high selectivity and low toxicity, according to the authors. The molecules have demonstrated high efficacy in killing cancer cells and low toxicity in non-tumor cells. Additionally, the process is achieved through 3 reaction stages by accessible starting materials and impressive yields.

The G-quadruplex is considered an emerging therapeutic target in oncology because of the key role it places in DNA replication and translation. The technology is particularly useful for pharmaceutical manufacturers in the oncology treatment landscape.

To-date, in vitro efficacy and toxicity studies have achieved positive results and are pending the start of clinical trials, according to the authors.

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