2021/12/08 by Mark Cushman · 1 citation
Biochemistry, Genetics and Molecular Biology · Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Cancer therapeutics and mechanisms #Bioactive Compounds and Antitumor Agents #Synthesis and biological activity
paper · doi:10.1021/acs.jmedchem.1c01491
openalex publication_date 2021/12/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The discovery that certain indenoisoquinolines inhibit the religation reaction of DNA in the topoisomerase I-DNA-indenoisoquinoline ternary complex led to a structure-based drug design research program which resulted in three representatives that entered Phase I clinical trials in cancer patients at the National Cancer Institute. This has stimulated a great deal of interest in the design and execution of new synthetic pathways for indenoisoquinoline production. More recently, modulation of the substitution pattern and chemical nature of substituents on the indenoisoquinoline scaffold has resulted in a widening scope of additional biological targets, including RXR, PARP-1, MYC promoter G-quadruplex, topoisomerase II, estrogen receptor, VEGFR-2, HIF-1α, and tyrosyl DNA phosphodiesterases 1 and 2. Furthermore, convincing evidence has been advanced supporting the potential use of indenoisoquinolines for the treatment of diseases other than cancer. The rapidly expanding indenoisoquinoline knowledge base has provided a firm foundation for further advancements in indenoisoquinoline chemistry, pharmacology, and therapeutics.