Ismail Noor Zafirah, Khairuddean Melati, Alidmat Mohammad Murwih, Abubakar Sadiq, Arsad Hasni
School of Chemical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia.
Faculty of Pharmacy, Jadara University, Irbid, 21110 Jordan.
3 Biotech. 2024 Jun;14(6):151. doi: 10.1007/s13205-024-03991-y. Epub 2024 May 10.
The study aims to investigate various aspects of synthesized mono-chalcone compounds and 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 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 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.
The online version contains supplementary material available at 10.1007/s13205-024-03991-y.
本研究旨在调查合成单查尔酮化合物与乳腺癌相关的各个方面，包括网络药理学、分子对接、分子动力学（MD）模拟、抗增殖作用和基因表达。最初，对这些化合物进行了针对乳腺癌相关靶点的网络药理学分析，通过MalaCards、SwissTargetPrediction和PharmMapper鉴定出70个乳腺癌靶标受体。随后，蛋白质-蛋白质相互作用（PPI）网络分析揭示了两个不同的靶基因簇。生存分析在京都基因与基因组百科全书（KEGG）富集和基因本体论（GO）评估后确定了七个重要靶基因。对这七个靶基因（AKT2、BRAF、ESR1、FGFR1、IGF1、IGF1R和KIT）进行了分子对接和MD模拟，结果表明化合物与靶向蛋白相互作用时表现出最高的结合亲和力，以及更好的稳定性和紧凑性。接下来，对这些化合物进行细胞活力测定和基因表达分析以验证计算机模拟结果。两种化合物均显示出抑制乳腺癌增殖的能力，化合物在靶向乳腺癌细胞时表现出更高的选择性，同时对正常乳腺细胞造成的损害最小。乳腺癌细胞增殖的抑制归因于AKT2、BRAF、FGFR1、IGF1、IGF1R、KIT和ESR1表达水平的降低。因此，这些结果为单查尔酮化合物抗乳腺癌能力的分子相互作用提供了见解。
在线版本包含可在10.1007/s13205-024-03991-y获取的补充材料。
