AI Article Synopsis
- A new method has been developed to synthesize a type of compound called C-ring substituted angular luotonins using a straightforward one-pot reaction involving specific chemicals.
- Research on these compounds showed they inhibit an enzyme called topoisomerase I (topo-I), but they are weaker inhibitors than camptothecin, a known drug.
- Interestingly, a different type of compound called tricyclic vasicinones was found to be more effective at inhibiting topo-I than the angular luotonins, suggesting potential for further study and development as new drugs.
Article Abstract
A facile one-pot synthesis of C-ring substituted angular luotonins has been realized via a methanesulfonic acid mediated aza-Nazarov-Friedlander condensation sequence on quinazolinonyl enones. Topoisomerase I (topo-I) inhibition studies revealed that the angular luotonin library (7a-7l) and their regioisomeric analogs (linear luotonins, 8a-8l) are weak negative modulators, compared to camptothecin. These results would fare well for the design of topo-I-inert luotonins for non-oncological applications such as anti-fungal and insecticide lead developments. Surprisingly, the tricyclic vasicinones (9h, 9i, and 9j) showed better topo-I inhibition compared to pentacyclic C-aryl luotonins providing a novel pharmacophore for further explorations.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113096 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2021.127998 | DOI Listing |
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