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Biological screening of cucurbitacin inspired estrone analogs targeting mitogen‐activated protein kinase (MAPK) pathway
Author(s) -
Ahmed Mahmoud S.,
ElSenduny Fardous,
Taylor Jessica,
Halaweish Fathi T.
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12963
Subject(s) - mapk/erk pathway , chemistry , protein kinase a , moiety , kinase , estrone , western blot , mtt assay , azide , cell culture , phosphorylation , biochemistry , microbiology and biotechnology , cell , stereochemistry , biology , genetics , organic chemistry , hormone , gene
Assembly of cucurbitacin inspired estrone analogs has been previously synthesized and screened against melanoma cell lines. Further synthetic optimization was executed via installation of Azide polar functional moiety across 23, 24 α, β‐unsaturated ketone side chain using Michael addition reaction. This was followed by biological screening against melanoma cell lines employing MTT assay, in‐cell‐based ELISA assay, and Western blot analysis to monitor the potential of the synthesized analogs to inhibit the phosphorylated ERK levels. This resulted in evolution of MH ‐4 possessing IC 50 of 3.59 μ m with significant decrease in the p‐ ERK and targeting MAPK pathway.