Rhodanine-Piperazine Hybrids as Potential VEGFR, EGFR, and HER2 Targeting Anti-Breast Cancer Agents

被引:0
|
作者
Szczepanski, Jacek [1 ]
Khylyuk, Dmytro [1 ]
Korga-Plewko, Agnieszka [2 ]
Michalczuk, Mariola [2 ]
Mandziuk, Slawomir [3 ]
Iwan, Magdalena [4 ]
Trotsko, Nazar [1 ]
机构
[1] Med Univ Lublin, Chair & Dept Organ Chem, 4A Chodzki St, PL-20093 Lublin, Poland
[2] Med Univ Lublin, Independent Med Biol Unit, 8b Jaczewski St, PL-20090 Lublin, Poland
[3] Med Univ Lublin, Dept Clin Oncol & Chemotherapy, 8 Jaczewski St, PL-20090 Lublin, Poland
[4] Med Univ Lublin, Dept Toxicol, 8B Jaczewski St, PL-20090 Lublin, Poland
关键词
rhodanine-piperazine hybrids; anti-breast cancer activity; molecular docking; VEGFR; EGFR; HER2; DRUG DISCOVERY; BIOLOGICAL EVALUATION; PERFORMANCE; ANTICANCER; MOLECULES; SCAFFOLD; DESIGN;
D O I
10.3390/ijms252212401
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Breast cancer is one of the most common malignancies affecting women worldwide, with a significant need for novel therapeutic agents to target specific molecular pathways involved in tumor progression. In this study, a series of rhodanine-piperazine hybrids were designed, synthesized, and evaluated for their anticancer activity, targeting key tyrosine kinases such as VEGFR, EGFR, and HER2. Biological screening against breast cancer cell lines (MCF-7, MDA-MB-231, T47D, and MDA-MB-468) revealed 3 of the 13 tested compounds as the most potent, with 5-({4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}methylidene)-2-thioxo-1,3-thiazolidin-4-one (12) showing the strongest activity, particularly against the MCF-7 and MDA-MB-468 cell lines. Molecular docking studies indicated favorable binding interactions of compound 12 and its 3-phenyl-2-thioxo-1,3-thiazolidin-4-one analogue (15) with HER2, VEGFR, and EGFR, and molecular dynamics simulations further confirmed their stable binding to HER2. These findings highlight the potential of rhodanine-piperazine hybrids as promising leads for developing new anticancer agents targeting breast cancer, particularly HER2-positive subtypes. Further structural optimization could enhance their efficacy and therapeutic profile.
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页数:22
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