New compounds identified as inhibitors of DNA topoisomerase 1

New compounds identified as inhibitors of DNA topoisomerase 1

The laboratory of Andrés Aguilera, in collaboration with that of Ralf Wellinger (both professors in the Department of Genetics at the University of Seville in Cabimer) and with Pharmamar, have identified two natural compounds, patulin and xestoquinol, as new inhibitors of the enzymes topoisomerase 1, a key element in the proper functioning of DNA. The finding published in the journalProceedings of the National Academy of Sciences of the United States of Americaopens new doors to understanding and treating diseases associated with damage to genetic material.

DNA topoisomerase 1 is an enzyme present in all organisms that is essential for cell proliferation. Its function is based on two catalytic steps: first cutting and then re-cutting the DNA, thereby relieving the topological stress generated during replication and transcription. Second, the inhibitors prevent the cuts in the DNA from ligating and leaving them open. In this way, they act as topoisomerase poisons and are used as anticancer drugs.

However, reliable inhibitors of the first step, DNA cleavage, are not available despite their potential in basic research and possible applications in medicine. According to this study, patulin and xestoquinol inhibit the first catalytic activity of topoisomerase I.in vitroin yeast and human cells.

The study, first authored by Emanuela Tumini, PhD, is published in the journalProceedings of the National Academy of Sciences of the United States of Americaand identifies a new class of inhibitors that open new perspectives in basic and cancer research.

The research was mainly funded by a government research agency RETOS project.

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