Investigating the potential of mono-chalcone compounds in targeting breast cancer receptors through network pharmacology, molecular docking, molecular dynamics simulation, antiproliferative effects, and gene expressions.

Autor: Ismail NZ; School of Chemical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia., Khairuddean M; School of Chemical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia., Alidmat MM; Faculty of Pharmacy, Jadara University, Irbid, 21110 Jordan., Abubakar S; School of Chemical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia.; Department of Pure and Industrial Chemistry, Bayero University Kano, Kano, 3011 Nigeria., Arsad H; Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang Malaysia.
Jazyk: angličtina
Zdroj: 3 Biotech [3 Biotech] 2024 Jun; Vol. 14 (6), pp. 151. Date of Electronic Publication: 2024 May 10.
DOI: 10.1007/s13205-024-03991-y
Abstrakt: The study aims to investigate various aspects of synthesized mono-chalcone compounds 5 and 8 concerning breast cancer, including network pharmacology, molecular docking, molecular dynamics (MD) simulations, antiproliferative effects, and gene expressions. Initially, the compounds underwent a network pharmacology analysis targeting breast cancer-related targets, with MalaCards, SwissTargetPrediction, and PharmMapper identifying 70 breast cancer target receptors. Subsequently, protein-protein interaction (PPI) network analysis revealed two distinct target gene clusters. Survival analysis identified seven significant target genes following Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) evaluation. Molecular docking and MD simulations were conducted on these seven target genes (AKT2, BRAF, ESR1, FGFR1, IGF1, IGF1R, and KIT), revealing that compound 8 exhibited the highest binding affinities, as well as better stability and compactness when interacting with the targeted proteins. Next, the compounds underwent cell viability assay and gene expression analysis to validate the in silico findings. Both compounds demonstrated the ability to suppress breast cancer proliferation, with compound 8 showing increased selectivity in targeting breast cancer cells while causing minimal harm to normal breast cells. The suppression of breast cancer cell proliferation was attributed to decreased expression levels of AKT2, BRAF, FGFR1, IGF1, IGF1R, KIT, and ESR1. Hence, the results provide insights into the molecular interaction responsible for the anti-breast cancer capabilities of mono-chalcone compounds.
Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03991-y.
Competing Interests: Conflict of interestNo potential conflict of interest was reported by the authors.
(© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
Databáze: MEDLINE
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