Melanoma is the most lethal type among skin cancers, causing about 75 % of all skin cancer deaths. B-Raf mutations show high incidence in melanoma. Inhibition of MEK can induce apoptosis. Inhibition of the MAPK signaling at any level can assist in the treatment of melanoma. A synthetic scheme for assembling a side chain possessing an a,�-unsaturated ketone at C17 of  ring D of estrone was executed, followed by  thiol Michael addition. Molecular docking study revealed the synthesized estrone analogs are competing with the ATP binding pocket at MEK. However, slight structural modifications on the estrone skeleton will lead to better binding affinity towards the non-ATP binding pocket. The first generation of the estrone analogs showed IC50 on A-375 cell lines, ranging from 19.70 to 31.84 �M. This prompted us to design the second generation of estrone analogs with a modification at C9 and C11 to be further evaluated in-vitro using MTT, ELISA, and ATP binding assays.

Design, synthesis, and biological evaluation of novel estrone analogs targeting MAPK pathway for the treatment of melanoma

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.