Development of Stable Amino-Pyrimidine–Curcumin Analogs: Synthesis, Equilibria in Solution, and Potential Anti-Proliferative Activity
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Published:2023-09-11
Issue:18
Volume:24
Page:13963
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Mari Matteo1, Boniburini Matteo1ORCID, Tosato Marianna12ORCID, Rigamonti Luca1ORCID, Cuoghi Laura3, Belluti Silvia3ORCID, Imbriano Carol3ORCID, Avino Giulia1, Asti Mattia2ORCID, Ferrari Erika1ORCID
Affiliation:
1. Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy 2. Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, Azienda USL-IRCCS Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy 3. Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/d, 41125 Modena, Italy
Abstract
With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate cancer cells. Unfortunately, these encouraging results were disappointing in vivo due to curcumin’s low stability and poor bioavailability. To overcome these issues, herein, the synthesis of eight new pyrimidine–curcumin derivatives is reported. The compounds were fully characterized (1H/13C NMR (Nuclear Magnetic Resonance), LC-MS (Liquid Chromatography-Mass Spectrometri), UV-Vis spectroscopy), particularly their acid/base behavior; overall protonation constants were estimated, and species distribution, as a function of pH, was predicted, suggesting that all the compounds are in their neutral form at pH 7.4. All the compounds were extremely stable in simulated physiological media (phosphate-buffered saline and simulated plasma). The compounds were tested in vitro (48 h incubation treatment) to assess their effect on cell viability in prostate cancer (LNCaP and PC3) and colorectal cancer (HT29 and HCT116) cell lines. Two compounds showed the same anti-proliferative activity as curcumin against HCT116 cells and improved cytotoxicity against PC3 cells.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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