Biological screening of cucurbitacin inspired estrone analogs targeting mitogen-activated protein kinase (MAPK) pathway.
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 IC50of 3.59 μm with significant decrease in the p-ERK and targeting MAPK pathway.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, El-Sherouk, Cairo, Egypt.
Mahmoud S
http://orcid.org/0000-0002-5600-4698
MS
Ahmed
Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt.
Fardous
F
El-Senduny
Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, USA.
Jessica
J
Taylor
Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, USA.
Fathi T
FT
Halaweish
D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054728:Cucurbitacins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis / Q000378:metabolism; D062105:Molecular Docking Simulation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000378:metabolism
D004970:Estrone; D054728:Cucurbitacins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
MAPK pathway; Michael addition; cucurbitacins; estrone; melanoma