Presentation Title

Synthesis of Amide Derivatives to Study Their Effect on the Wnt Signaling Pathway

Faculty Mentor

Peter de Lijser

Start Date

23-11-2019 8:00 AM

End Date

23-11-2019 8:45 AM

Location

245

Session

poster 1

Type of Presentation

Poster

Subject Area

physical_mathematical_sciences

Abstract

The Wnt/β-catenin pathway takes part in the regulation of gene expression. The pathway causes an accumulation of β-catenin, which then moves to the nucleus where it acts as a transcription cofactor. When the pathway is turned off, β-catenin is destroyed by a protein complex. The Wnt signaling pathway and elevated levels of β-catenin are involved in stem cell pluripotency and the progression of cancer. Small organic molecules were designed and synthesized to inhibit the Wnt pathway. Previous work has shown that molecules containing amide groups are effective at reducing β-catenin levels and decrease cell proliferation in cervical cancer cells. Molecules containing bulky groups such as t-butyl were shown to decrease cell proliferation. For our current work, we have designed a new library of compounds to further explore these characteristics. Compounds were purified using column chromatography and analyzed using NMR. Biological analysis was done using CyQUANT cell proliferation assays. Preliminary data suggests that molecules with larger phenyl groups were not as effective at decreasing cell proliferation compared to drugs with t-butyl groups. A compound with an ester group and halogens, SGGR2, was shown to consistently decrease cell proliferation and generally work better than other molecules used in this study so far. Molecules similar to SGGR2 will be synthesized to expand on the library of potential anticancer drugs. Molecules that can reduce β-catenin levels and decrease cell proliferation in cervical cancer cells show potential for a cancer therapy.

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Nov 23rd, 8:00 AM Nov 23rd, 8:45 AM

Synthesis of Amide Derivatives to Study Their Effect on the Wnt Signaling Pathway

245

The Wnt/β-catenin pathway takes part in the regulation of gene expression. The pathway causes an accumulation of β-catenin, which then moves to the nucleus where it acts as a transcription cofactor. When the pathway is turned off, β-catenin is destroyed by a protein complex. The Wnt signaling pathway and elevated levels of β-catenin are involved in stem cell pluripotency and the progression of cancer. Small organic molecules were designed and synthesized to inhibit the Wnt pathway. Previous work has shown that molecules containing amide groups are effective at reducing β-catenin levels and decrease cell proliferation in cervical cancer cells. Molecules containing bulky groups such as t-butyl were shown to decrease cell proliferation. For our current work, we have designed a new library of compounds to further explore these characteristics. Compounds were purified using column chromatography and analyzed using NMR. Biological analysis was done using CyQUANT cell proliferation assays. Preliminary data suggests that molecules with larger phenyl groups were not as effective at decreasing cell proliferation compared to drugs with t-butyl groups. A compound with an ester group and halogens, SGGR2, was shown to consistently decrease cell proliferation and generally work better than other molecules used in this study so far. Molecules similar to SGGR2 will be synthesized to expand on the library of potential anticancer drugs. Molecules that can reduce β-catenin levels and decrease cell proliferation in cervical cancer cells show potential for a cancer therapy.