Cited by 21Synthesis and biological activityComputational Drug Discovery MethodsSynthesis of Organic Compounds

Developing multitarget coumarin based anti-breast cancer agents: synthesis and molecular modeling study

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Takla, Fiby N., Bayoumi, Waleed A., El-Messery, Shahenda M., Nasr, Magda N. A.·2023·Scientific Reports

Abstract

A new series of 7-substituted coumarin scaffolds containing a methyl ester moiety at the C 4-position were synthesized and tested for their in vitro anti-proliferative activity against MCF-7 and MDA-MB-231 breast cancer cell lines using Doxorubicin (DOX) as reference. Compounds 2 and 8 showed noticeable selectivity against MCF-7 with IC 50 = 6.0 and 5.8 µM, respectively compared to DOX with IC 50 = 5.6 µM. Compounds 10, 12, and 14 exhibited considerable selectivity against Estrogen Negative cells with IC 50 = 2.3, 3.5, and 1.9 µM, respectively) compared to DOX with (IC 50 = 7.3 µM). The most promising compounds were tested as epidermal growth factor receptor and aromatase (ARO) enzymes inhibitors using erlotinib and exemestane (EXM) as standards, respectively. Results proved that compound 8 elicited the highest inhibitory activity (94.73% of the potency of EXM), while compounds 10 and 12 displayed 97.67% and 81.92% of the potency of Erlotinib, respectively. Further investigation showed that the promising candidates 8, 10, and 12 caused cell cycle arrest at G0–G1 and S phases and induced apoptosis. The mechanistic pathway was confirmed by elevating caspases-9 and Bax/Bcl-2 ratio. A set of in silico methods was also performed including docking, bioavailability ADMET screening and QSAR study

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Crossref · 10.1038/s41598-023-40232-3

Cites

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  • Both extraction methods agree on the absence of coumarins.

    “Both extraction methods agree on the absence of coumarins, confirmed by the negative result in the NaOH test [30].”

    From Comparative Analysis of Infusions and Ethanolic Extracts of Annona muricata Leaves from Colima, Mexico: Phytochemical Profile and Antioxidant Activity (2024) · cites this paper as [30]

    The Results > Chemistry section describes synthesizing coumarin derivatives and confirming their structures by spectroscopy; it does not assess coumarins in extracts. Searches for extraction methods, phytochemical screening, and a negative NaOH test found no passage addressing the claim. The synthesized compounds do not establish whether coumarins were absent from the extracts in question. (LLM, conf=0.75)

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Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 2

  1. [33]Ragab FA Synthesis and biological evaluation of new coumarin derivatives as cytotoxic agents Arch. der Pharm. 2021 354 8 e2100029 10.1002/ardp.202100029 33872414 · DOI
  2. [34]Stefanachi A Design, synthesis, and biological evaluation of imidazolyl derivatives of 4,7-disubstituted coumarins as aromatase inhibitors selective over 17-α-hydroxylase/C17–20 lyase J. Med. Chem. 2011 54 6 1613 1625 10.1021/jm101120u 21341743 · DOI

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Authors
Takla, F. N., Bayoumi, W. A., El-Messery, S. M., & Nasr, M. N. A.
Affiliations
Mansoura University (EG)
Venue
Scientific Reports
Published
2023-08-17
Volume
13
Issue
1
Pages
13370-13370
ISSN
2045-2322 (ISSN-L)
OpenAlex
W4385954212
Cited by
21
References
50
Citations by year
2026: 5 · 2025: 7 · 2024: 8 · 2023: 1
FWCI
2.14
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Mansoura University
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Health Sciences › Medicine › Pharmacology › Synthesis of Organic Compounds
Keywords
coumarins, breast cancer, MCF-7 cells, MDA-MB-231 cells, EGFR inhibitors, aromatase inhibitors, cell cycle arrest, apoptosis, caspase-9, Bax/Bcl-2 ratio, QSAR, ADMET prediction, multitarget anticancer agents
MeSH terms
Erlotinib Hydrochloride, Antineoplastic Agents, Coumarins, Doxorubicin, Neoplasms, Aromatase Inhibitors

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