PXD065576

PXD065576 is an original dataset announced via ProteomeXchange.

Title	Investigating the multi-mechanistic anticancer effects of 4-bisarylurea thiouracil derivatives in breast cancer cells
Description	The study reports the synthesis of a series of 4-bisarylureathiouracil derivatives (6a-e) for potential use in breast cancer treatment. In vitro cytotoxicity was assessed in MCF-7 and MDA-MB-231 human breast cancer cell lines, revealing significant anti-cancer activity. Compound 6e exhibited the highest cytotoxicity, with IC50 values of 7.94 μM for MCF-7 and 6.67 μM for MDA-MB-231, although it was also the most toxic to RAW 264.7 macrophage cells. In contrast, compound 6c demonstrated strong efficacy against both cancer cell lines (IC50 = 9.23 ± 0.6 μM for MCF-7 and 7.72 ± 0.6 μM for MDA-MB-231) while maintaining selectivity (SI values >10.8 and > 12.9, respectively). Flow cytometry and caspase-3 assays indicated that compounds 6a-c induced apoptosis in MCF-7 cells. In anti-inflammatory assays, compounds 6a and 6d showed significant effects, while 6c demonstrated the weakest, suggesting its cytotoxicity is not linked to anti-inflammatory properties. Compound 6c was prioritised for further investigation because of its preferential targeting of cancer cells. Proteomic analysis of 6c-treated cells revealed significant dysregulation of apoptosis, angiogenesis and VEGF signalling, Rho signal transduction, and pi3k-akt signalling pathways. These findings highlighted the potential of compounds 6a-e as effective anticancer agents, warranting further investigation and optimization for therapeutic applications.
HostingRepository	PRIDE
AnnounceDate	2025-07-19
AnnouncementXML	Submission_2025-07-19_04:20:50.570.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD065576
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Muhammad Alsherbiny
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-28 04:00:50	ID requested
⏵ 1	2025-07-19 04:20:51	announced

10.1016/j.bioorg.2025.108581;

10.6019/PXD065576;

10.1016/J.BIOORG.2025.108581;

Fares M, Alsherbiny M, Elkelesh IA, Said MA, Maklad RM, Lewis W, Li CG, Eldehna WM, Groundwater PW, Gale PA, Keller PA, Investigating the multi-mechanistic anticancer effects of 4-bisarylurea thiouracil derivatives in breast cancer cells. Bioorg Chem, 162():108581(2025) [pubmed]

submitter keyword: Apoptosis, Anti-inflammatory,Breast cancer, Cytotoxicity, Proteomics

Mohamed Fares
contact affiliation	Sydney Pharmacy School, The University of Sydney, NSW 2006, Australia
contact email	mohamed.metwaly@sydney.edu.au
lab head
Muhammad Alsherbiny
contact affiliation	1) Freedman Foundation Metabolomics Facility, Innovation Centre, Victor Chang Cardiac Research Institute UNSW 2) Pharmacognosy Department, Faculty of Pharmacy, Cairo University
contact email	muhammad.alsherbiny@pharma.cu.edu.eg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065576
     1. Label: PRIDE project
     2. Name: Investigating the multi-mechanistic anticancer effects of 4-bisarylurea thiouracil derivatives in breast cancer cells