Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity
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2021
Authors
Tadić, JulijanaLađarević, Jelena
Vitnik, Zeljko J.
Vitnik, Vesna D.
Stanojkovic, Tatjana P.
Matic, Ivana Z.
Mijin, Dušan
Article (Published version)
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Seven novel azo dyes with 2-pyridone and dihydropyrimidinone moieties have been synthesized and thoroughly characterized. The azo-hydrazone tautomerism has been investigated by experimental and theoretical approaches. The optimizations of geometries have been performed with density functional theory (DFT). The vibrational and NMR spectra were calculated and correlated with experimental ones. Furthermore, quantum chemical descriptors were calculated and MEP maps were plotted to determine biological reactivity of dyes. The antioxidant assay evinced that 5, 6 and 7 are promising antioxidant candidates. In vitro cytotoxic activity was studied against three malignant cell lines: prostate adenocarcinoma (PC-3), lung carcinoma (A549) and chronic myelogenous leukemia (K562), as well as against human normal lung fibroblasts (MRC-5), using MTT assay. Examination of cytotoxic effects on human cancer cell lines showed the concentration dependent cytotoxicity of all investigated compounds. The K562... cells were the most sensitive to the cytotoxicity of the compounds 3, 5 and 6, wherein compound 5 was particularly prominent and selective in cytotoxic action between K562 (24.97 mu M) and PC-3 (48.98 mu M) cancer cells, and normal MRC-5 (91.11 mu M) cells. Moreover, the cell cycle analysis of compound 5 was examined in K562 cells, by flow cytometry, to study its mechanism of anticancer action. Finally, in silico evaluation of physicochemical parameters, druglikeness and ADME properties showed that investigated compounds are orally bioavailable with no permeation to the blood brain barrier.
Keywords:
Biginelli adduct / Azo-hydrazone tautomerism / Antitumor / Cell cycle arrest / ADMESource:
Dyes and Pigments, 2021, 187Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-MESTD-inst-2020-200026)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200135 (University of Belgrade, Faculty of Technology and Metallurgy) (RS-MESTD-inst-2020-200135)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200287 (Innovation Center of the Faculty of Technology and Metallurgy) (RS-MESTD-inst-2020-200287)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200043 (Institute of Oncology and Radiology of Serbia, Belgrade) (RS-MESTD-inst-2020-200043)
DOI: 10.1016/j.dyepig.2020.109123
ISSN: 0143-7208
WoS: 000618738600003
Scopus: 2-s2.0-85098647658
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Inovacioni centarTY - JOUR AU - Tadić, Julijana AU - Lađarević, Jelena AU - Vitnik, Zeljko J. AU - Vitnik, Vesna D. AU - Stanojkovic, Tatjana P. AU - Matic, Ivana Z. AU - Mijin, Dušan PY - 2021 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4895 AB - Seven novel azo dyes with 2-pyridone and dihydropyrimidinone moieties have been synthesized and thoroughly characterized. The azo-hydrazone tautomerism has been investigated by experimental and theoretical approaches. The optimizations of geometries have been performed with density functional theory (DFT). The vibrational and NMR spectra were calculated and correlated with experimental ones. Furthermore, quantum chemical descriptors were calculated and MEP maps were plotted to determine biological reactivity of dyes. The antioxidant assay evinced that 5, 6 and 7 are promising antioxidant candidates. In vitro cytotoxic activity was studied against three malignant cell lines: prostate adenocarcinoma (PC-3), lung carcinoma (A549) and chronic myelogenous leukemia (K562), as well as against human normal lung fibroblasts (MRC-5), using MTT assay. Examination of cytotoxic effects on human cancer cell lines showed the concentration dependent cytotoxicity of all investigated compounds. The K562 cells were the most sensitive to the cytotoxicity of the compounds 3, 5 and 6, wherein compound 5 was particularly prominent and selective in cytotoxic action between K562 (24.97 mu M) and PC-3 (48.98 mu M) cancer cells, and normal MRC-5 (91.11 mu M) cells. Moreover, the cell cycle analysis of compound 5 was examined in K562 cells, by flow cytometry, to study its mechanism of anticancer action. Finally, in silico evaluation of physicochemical parameters, druglikeness and ADME properties showed that investigated compounds are orally bioavailable with no permeation to the blood brain barrier. T2 - Dyes and Pigments T1 - Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity VL - 187 DO - 10.1016/j.dyepig.2020.109123 ER -
@article{ author = "Tadić, Julijana and Lađarević, Jelena and Vitnik, Zeljko J. and Vitnik, Vesna D. and Stanojkovic, Tatjana P. and Matic, Ivana Z. and Mijin, Dušan", year = "2021", abstract = "Seven novel azo dyes with 2-pyridone and dihydropyrimidinone moieties have been synthesized and thoroughly characterized. The azo-hydrazone tautomerism has been investigated by experimental and theoretical approaches. The optimizations of geometries have been performed with density functional theory (DFT). The vibrational and NMR spectra were calculated and correlated with experimental ones. Furthermore, quantum chemical descriptors were calculated and MEP maps were plotted to determine biological reactivity of dyes. The antioxidant assay evinced that 5, 6 and 7 are promising antioxidant candidates. In vitro cytotoxic activity was studied against three malignant cell lines: prostate adenocarcinoma (PC-3), lung carcinoma (A549) and chronic myelogenous leukemia (K562), as well as against human normal lung fibroblasts (MRC-5), using MTT assay. Examination of cytotoxic effects on human cancer cell lines showed the concentration dependent cytotoxicity of all investigated compounds. The K562 cells were the most sensitive to the cytotoxicity of the compounds 3, 5 and 6, wherein compound 5 was particularly prominent and selective in cytotoxic action between K562 (24.97 mu M) and PC-3 (48.98 mu M) cancer cells, and normal MRC-5 (91.11 mu M) cells. Moreover, the cell cycle analysis of compound 5 was examined in K562 cells, by flow cytometry, to study its mechanism of anticancer action. Finally, in silico evaluation of physicochemical parameters, druglikeness and ADME properties showed that investigated compounds are orally bioavailable with no permeation to the blood brain barrier.", journal = "Dyes and Pigments", title = "Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity", volume = "187", doi = "10.1016/j.dyepig.2020.109123" }
Tadić, J., Lađarević, J., Vitnik, Z. J., Vitnik, V. D., Stanojkovic, T. P., Matic, I. Z.,& Mijin, D.. (2021). Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity. in Dyes and Pigments, 187. https://doi.org/10.1016/j.dyepig.2020.109123
Tadić J, Lađarević J, Vitnik ZJ, Vitnik VD, Stanojkovic TP, Matic IZ, Mijin D. Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity. in Dyes and Pigments. 2021;187. doi:10.1016/j.dyepig.2020.109123 .
Tadić, Julijana, Lađarević, Jelena, Vitnik, Zeljko J., Vitnik, Vesna D., Stanojkovic, Tatjana P., Matic, Ivana Z., Mijin, Dušan, "Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity" in Dyes and Pigments, 187 (2021), https://doi.org/10.1016/j.dyepig.2020.109123 . .