Biological screening of cucurbitacin inspired estrone analogs targeting mitogen-activated protein kinase (MAPK) pathway

Mahmoud S. Ahmed; Fardous El-Senduny; Jessica Taylor; Fathi T. Halaweish

doi:10.1111/cbdd.12963

Biological screening of cucurbitacin inspired estrone analogs targeting mitogen-activated protein kinase (MAPK) pathway

Mahmoud S. Ahmed, Fardous El-Senduny, Jessica Taylor, Fathi T. Halaweish

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

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 IC₅₀ of 3.59 μm with significant decrease in the p-ERK and targeting MAPK pathway.

Original language	English (US)
Pages (from-to)	478-484
Number of pages	7
Journal	Chemical Biology and Drug Design
Volume	2017
DOIs	https://doi.org/10.1111/cbdd.12963
State	Published - 2017
Externally published	Yes

Keywords

Cucurbitacins
Estrone
MAPK pathway
Melanoma
Michael addition

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
Organic Chemistry

Access to Document

10.1111/cbdd.12963

Cite this

@article{fc7e960b82e04bc1ac81207c6951c749,

title = "Biological screening of cucurbitacin inspired estrone analogs targeting mitogen-activated protein kinase (MAPK) pathway",

abstract = "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 IC50 of 3.59 μm with significant decrease in the p-ERK and targeting MAPK pathway.",

keywords = "Cucurbitacins, Estrone, MAPK pathway, Melanoma, Michael addition",

author = "Ahmed, {Mahmoud S.} and Fardous El-Senduny and Jessica Taylor and Halaweish, {Fathi T.}",

note = "Publisher Copyright: {\textcopyright} 2017 John Wiley & Sons A/S.",

year = "2017",

doi = "10.1111/cbdd.12963",

language = "English (US)",

volume = "2017",

pages = "478--484",

journal = "Chemical Biology and Drug Design",

issn = "1747-0277",

publisher = "Blackwell",

}

TY - JOUR

T1 - Biological screening of cucurbitacin inspired estrone analogs targeting mitogen-activated protein kinase (MAPK) pathway

AU - Ahmed, Mahmoud S.

AU - El-Senduny, Fardous

AU - Taylor, Jessica

AU - Halaweish, Fathi T.

PY - 2017

Y1 - 2017

N2 - 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 IC50 of 3.59 μm with significant decrease in the p-ERK and targeting MAPK pathway.

AB - 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 IC50 of 3.59 μm with significant decrease in the p-ERK and targeting MAPK pathway.

KW - Cucurbitacins

KW - Estrone

KW - MAPK pathway

KW - Melanoma

KW - Michael addition

UR - http://www.scopus.com/inward/record.url?scp=85020562769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020562769&partnerID=8YFLogxK

U2 - 10.1111/cbdd.12963

DO - 10.1111/cbdd.12963

M3 - Article

C2 - 28171685

AN - SCOPUS:85020562769

SN - 1747-0277

VL - 2017

SP - 478

EP - 484

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

ER -

Biological screening of cucurbitacin inspired estrone analogs targeting mitogen-activated protein kinase (MAPK) pathway

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this