AI Article Synopsis
- Researchers are exploring new chemical structures (chemotypes) to create inhibitors for topoisomerase I (Top1) enzymes, targeting cancer treatment.
- The pyrazolo[1,5-a]quinazoline structure, similar to an existing effective compound, was modified with different chemical groups to produce various Top1 inhibitors.
- The effectiveness of these inhibitors was analyzed using structure-activity relationship (SAR) data and advanced docking techniques to evaluate how they interact with the enzyme.
Article Abstract
In search for a novel chemotype to develop topoisomerase I (Top1) inhibitors, the pyrazolo[1,5-a]quinazoline nucleus, structurally related to the indenoisoquinoline system precursor of well-known Top1 poisons, was variously decorated (i.e., a substituted phenyl ring at 2- or 3-position, a protonable side chain at 4- or 5-position), affording a number of Top1 inhibitors with cleavage patterns common to CPT and MJ-III-65. SARs data were rationalized by means of an advanced docking protocol.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982121 | PMC |
| http://dx.doi.org/10.1021/jm400932c | DOI Listing |
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