Developing multitarget coumarin based anti-breast cancer agents: synthesis and molecular modeling study
Open accessAbstract
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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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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- 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)
- PMC
- PMC10435442
- 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
- gold
- doi.org
- 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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