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Abstract 2059 Flow Synthesis and Cancer Cell Cytotoxicity of Caffeic Acid Phenethyl Amide (CAPA) Derivatives

2024; Elsevier BV; Volume: 300; Issue: 3 Linguagem: Inglês

10.1016/j.jbc.2024.106118

1083-351X

Muppidi Subbarao, Mauricio Jemal, Anthony Saucedo, Nakya Mesa‐Diaz, Jadyn L. Smith, Liqin Du, Sean M. Kerwin,

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Abstract: Caffeic acid phenethyl ester (CAPE) is a phenolic natural product with a wide range of biological activities including anticancer activity; however, the ester group of CAPE is metabolically labile. The corresponding amide CAPA has improved metabolic stability, but diminished anticancer activity relative to CAPE. The objective of this study is to determine if analogues of CAPA can be prepared that recapture the anticancer activity of CAPE while retaining the metabolic stability of CAPA. To address this objective, we carried out the synthesis of CAPA analogues both in batch and using a flow Wittig reaction approach to prepare of a series of previously reported and novel CAPA analogues, and conducted in vitro cancer cell cytoxicity assays on these compounds. Here we report that the batch and flow Wittig reactions proceed with good stereochemical selectivity; however, the overall yields for the batch approach is superior. Cytotoxicity studies of CAPE, CAPA and these CAPA analogues in HeLa and BE(2)-C cells were carried out. The diminished cytotoxicity of CAPA compared to CAPE was confirmed in these assays; however, one novel CAPA analogue was identified as having cytotoxic activity similar to CAPE in HeLa cells, albeit with lower activity against BE(2)-C cells than CAPA. In conclusion, we show here that analogues of CAPA can display in vitro anticancer activity that is comparable to CAPE, at least in one cancer cell line. We have also shown an unexpected activity of CAPA itself on the BS(2)-C neuroblastoma cell line. Future work establishing the structure-activity relationship for the anticancer activity oof CAPA analogues is on-going. Keywords: anticancer; natural product; CAPE; CAPA; Wittig reaction; flow chemistry Acknowledgements: This work was supported by the NIH Bridges to the Baccalaureate program GM107759, NSF grant CHE-1955432, and the Partnership for Research and Education in Materials (PREM) NSF Grant DMR-2122041.