Synlett
DOI: 10.1055/a-2500-7537
letter
Small Molecules in Medicinal Chemistry

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

Halil Şenol
a   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Fatih, Istanbul, Turkey
,
Zeynep Çağman
b   Department of Biochemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Fatih, Istanbul, Turkey
,
Furkan Çakır
a   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Fatih, Istanbul, Turkey
,
Feyzi Sinan Tokalı
c   Department of Material and Material Processing Technologies, Kars Vocational School, Kafkas University, 36100 Kars, Turkey
› Author Affiliations


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.

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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