Genomic DNA, which is organized around double-stranded B-form DNA, is both durable and flexible enough to store and pass on genetic information. Once freed from the associations of an extended complimentary sequence, single stranded DNA and RNA can adopt a vast array of other stable secondary structure motifs ideal for its involvement in other biological settings other than as a store of genetic information. Guanine-rich nucleic acids can fold into distinctive four-stranded conformers found in telomeric DNA repeats (i.e. TTAGGG), also known as G-quadruplexes (G4), as well as in sequences in the promoter and other regulatory regions of genes (i.e. <i>c-myc</i>), especially those involved in cellular proliferation. Small molecules that induce the formation of, and/or selectively bind to, G-quadruplex structures are of interest for development as potential therapeutic agents, particularly in the anticancer therapeutic area. To date, quarfloxin is the only G-quadruplex ligand that has progressed to clinical evaluation. Novel 10-oxy-substituted AIM derivatives were synthesized and will be presented. The isoxazole functionality establishes not only a pre-organized system for SAR exploration it is the biological handle that is the foundation of many medicines used in general medical practice today, and therefore should be a potent contender in the pool of small molecule antitumor agents. They have been evaluated for biological activity and cytotoxicity against SNB-19 CNS glioblastoma cells. The synthesis, characterization, biological studies, and future directions will be presented

10-oxy-anthracenyl isoxazole amides (AIMs) as potential G-quadruplex stabilizing antitumor agents

249th National Meeting (2015)

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