Abstract

DNA topoisomerases play a critical role as essential enzymes in controlling alterations in the topology of DNA. They achieve this by orchestrating the coordinated process of breaking and rejoining DNA strands, which is crucial for maintaining the proper structure of DNA during regular cellular development. The search for and development of new potential anticancer drugs is a challenging yet immensely important area of research that can contribute significantly to advancements in the treatment and combat of cancer-related diseases. In the scope of my doctoral work, research was conducted on three heterocyclic compounds derived from carbazole, aiming to identify their anticancer mechanism of action. The studies demonstrated that these compounds act as non-intercalating DNA inhibitors of human topoisomerase I and IIα. Among the three investigated compounds, 36a exhibited notably higher inhibitory activity against the IIα isoform compared to IIβ. Additionally, their cytotoxic and antiproliferative properties were determined, along with their ability to inhibit tyrosine protein kinases and induce cell death. The conducted experiments allowed to determine the main mechanisms of action of these anticancer compounds, which could in the future contribute to the design and synthesis of new potential drug candidates.

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