article · Scientific Reports
A new series of pyrazole-thiazol-4-one hybrid compounds, designated 9a to 9p, has been synthesised and evaluated as potential anticancer therapeutics targeting oncogenic proteins. In laboratory tests, all the synthesised molecules demonstrated antiproliferative activity against two breast cancer cell lines, T-47D and MDA-MB-231. The two most effective compounds, 9g and 9k, were further examined for their ability to inhibit epidermal growth factor receptor (EGFR). Both candidates showed inhibitory activity at nanomolar concentrations, with half-maximal inhibitory concentrations of 267 and 395 nanomolar, respectively. Further biological testing revealed that compounds 9g and 9k triggered programmed cell death (apoptosis) in MDA-MB-231 breast cancer cells and caused cell cycle arrest at the G2/M phase. Complementary computational analyses, including molecular docking and molecular dynamics simulations, were also conducted to examine how these molecules interact with their biological targets.
Breast cancer remains a major global health challenge, driving continuous demand for treatments that selectively target proteins responsible for tumour progression and survival. By inhibiting the epidermal growth factor receptor and halting cancer cell proliferation, these newly designed chemical hybrids offer useful starting points for developing targeted therapies that could potentially improve cancer care.
This work represents early-stage drug discovery, confined to in vitro cell assays and computer simulations. The findings could interest medicinal chemists and oncology pharmaceutical developers seeking lead compounds for epidermal growth factor receptor inhibition. Significant development, including comprehensive toxicity screening, in vivo animal testing, and pharmacokinetic studies, will be required before these compounds can advance towards preclinical development or therapeutic use.
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Abstract Currently, the humanity is in a fierce battle against various health-related challenges especially those associated with human malignancies. This created the urge to develop potent and selective inhibitors for tumor cells through targeting specific oncogenic proteins possessing crucial roles in cancer progression and survive. In this respect, new series of pyrazole-thiazol-4-one hybrids ( 9a–p ) were synthesized as potential anticancer agents. All the synthesized molecules exhibited potent antiproliferative actions against breast cancer (BC) T-47D and MDA-MB-231 cell lines with IC 50 ranges 3.14–4.92 and 0.62–58.01, respectively. Moreover, the most potent anti-proliferative counterparts 9g and 9k were assessed against EGFR. They displayed nanomolar inhibitory activity, IC 50 267 ± 12 and 395 ± 17 nM, respectively. Worth noting, both compounds 9g and 9k induced apoptosis in MDA-MB-231 cells, and resulted in a cell cycle arrest at G2/M phase. Furthermore, an in silico analysis including docking and molecular dynamic simulations was performed.
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DOI: 10.1038/s41598-022-15050-8
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