article · Pharmaceuticals
Researchers designed and synthesised three groups of chemical compounds based on cyanopyridone structures. These molecules were evaluated in the laboratory for their capacity to halt the growth of breast adenocarcinoma and liver cancer cell lines. Several of the newly created compounds demonstrated higher potency against the tested cancer cells than the conventional chemotherapy drug taxol. In particular, two specific compounds, designated 5a and 5e, exhibited the strongest antiproliferative activity against breast cancer cells, while compounds 6b and 5a performed best against liver cancer cells. Further biological assessment of the leading breast cancer inhibitors revealed their capacity to inhibit VEGFR-2 and HER-2, two enzymes heavily involved in tumour progression. Computational docking and molecular dynamics simulations clarified how these compounds interact with their target receptors, providing structural insight into their biological activity.
Cancer treatments often face challenges such as drug resistance and limited effectiveness. Discovering molecules that simultaneously inhibit two disease pathways, such as VEGFR-2 and HER-2, offers potential routes for developing multi-target cancer therapies. Demonstrating that laboratory-synthesised compounds outperform conventional drugs like taxol in cell cultures marks a useful starting point for identifying new candidate molecules in oncology drug discovery.
This research represents early-stage laboratory drug discovery that could interest pharmaceutical developers and oncology researchers seeking new chemical leads. The work demonstrates in vitro cell inhibition and computational target engagement. However, the molecules remain far from clinical or commercial use, requiring extensive follow-up investigations including in vivo animal testing, safety profiling, and pharmacokinetic optimisation before any therapeutic development pathway can proceed.
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In the current work, we designed and synthesized three families of non-fused and fused compounds based on cyanopyridone: derivatives of 6-amino-1,2-dihydropyridine-3,5-dicarbonitrile (5a-f) and 3,4,7,8-tetrahydro pyrimidine-6-carbonitrile (6a-b and 7a-e). The newly synthesized compounds’ structure were determined using a variety of techniques, including 1H NMR, 13C NMR, mass spectrum, infrared spectroscopy, and elemental analysis. The developed compounds were tested for the ability to inhibit the growth of breast adenocarcinoma (MCF-7) and hepatic adenocarcinoma (HepG2) cell lines using MTT assay. Some of the synthesized compounds were more effective towards the cancer cell lines than the standard treatment taxol. The best antiproliferative activities were demonstrated by non-fused cyanopyridones 5a and 5e against the MCF-7 cell line (IC50 = 1.77 and 1.39 μM, respectively) and by compounds 6b and 5a against the HepG2 cell line (IC50 = 2.68 and 2.71 μM, respectively). We further explored 5a and 5e, the two most potent compounds against the MCF-7 cell line, for their ability to inhibit VEGFR-2 and HER-2. Finally, docking and molecular dynamics simulations were performed as part of the molecular modeling investigation to elucidate the molecular binding modes of the tested compounds, allowing for a more thorough comprehension of the activity of compounds 5a and 5e.
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DOI: 10.3390/ph15101262
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