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DOI: 10.1055/a-2500-7537
Synthesis, Characterization, and In Vitro and In Silico Biological Evaluation of Novel Polyphenols Bearing a Quinazolin-4(3H)-one Ring as Promising Anti-Prostate-Cancer Agents
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Abstract
In this study, 12 novel polyphenols containing the quinazolin-4(3H)-one ring were synthesized and characterized using 1H/13C NMR and HRMS analyses, yielding the target compounds in excellent yields (88–96%). Biological evaluation revealed significant cytotoxic activity against PC3 prostate cancer and 3T3 fibroblast cell lines, with compounds 2,2′-(propane-1,3-diyl)bis-3-(2,4-dihydroxybenzylideneamino)quinazolin-4(3H)-one (5) and 2,2′-(propane-1,3-diyl)bis-3-(2,3,4-trihydroxybenzylideneamino)quinazolin-4(3H)-one (6) demonstrating the highest anticancer potential. Compound 6 exhibited the highest selectivity (IC50 = 5.72 µM, SI = 68), outperforming the reference drug, doxorubicin. In silico studies, including molecular docking and dynamics simulations, showed strong binding affinities for mTOR, P110α, and PARP1, particularly for compound 6. Key interactions, such as hydrogen bonds and π-π stacking, contributed to the stability of the 6–mTOR complex. These results highlight compounds 5 and 6 as promising candidates for prostate cancer therapy, with compound 6 showing superior selectivity and interaction profiles, providing the groundwork for further preclinical development.
Key words
hydrazone - quinazolin-4(3H)-one - prostate cancer - cytotoxicity - molecular docking - molecular dynamicsSupporting Information
- The experimental sections for the chemistry, biological activity and computational studies, along with the experimental data for the remaining compounds, are available in the supporting material. This includes the spectral data for all compounds, inhibition graphs, and molecular docking and dynamics figures for the other molecules. The biological activity 10 and computational studies 11 were conducted by following the methodology published in our previous works.Supporting information for this article is available online at https://doi.org/10.1055/a-2500-7537.
- Supporting Information
Publication History
Received: 15 October 2024
Accepted after revision: 11 December 2024
Accepted Manuscript online:
11 December 2024
Article published online:
17 January 2025
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