Synthesis and Biological Activity of Novel Antimitotic Agents
- Detailed Technology Description
- None
- *Abstract
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The spiroketal pentacyclic palmarumycins are structurally unique natural products with both antifungal and antibacterial activities. The inventors have synthesized a small collection of novel palmarumycin analogs by a parallel synthetic strategy. Several of these compounds including [8-(furan-3-ylmethoxy)-1-oxo-1,4-dihydronaphthalene-4-spiro-2'-naphtho[1",8"-de][1',3']dioxin] or SR-7 inhibit the proliferation of human MCF-7 and MDA-MB-231 breast cancer cells and increase the mitotic marker phosphohistone H3. SR-7 prominently blocks cell cycle transition in G2/M phase. SR-7 also causes almost equal inhibition in the growth of paclitaxel-sensitive and resistant cells. Morphological analyses of MCF-7 cells treated with SR-7 indicate a unique disruption of tubulin architecture that may be responsible for the G2/M arrest. Unlike benchmark tubulin disrupting agents, however, SR-7 does not cause hyperphosphorylation of the anti-apoptotic protein Bcl-2. Thus, SR-7 represents a novel, minimal, pharmacologically active chemical structure with unusual growth inhibitory attributes. This compound or structurally similar compounds may be useful as anticancer agents.
- *Principal Investigator
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Name: Billy Day
Department: Pharm-Pharmaceutical Science
Name: John Lazo
Department: Departments of Pharmacology & Chemistry
Name: Peter Wipf
Department: Chemistry
- Country/Region
- USA
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