Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity
Samo za registrovane korisnike
2021
Autori
Tadić, Julijana D.Lađarević, Jelena
Vitnik, Željko
Vitnik, Vesna
Stanojković, Tatjana
Matić, Ivana Z.
Mijin, Dušan
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 compo...unds. 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 μM) and PC-3 (48.98 μM) cancer cells, and normal MRC-5 (91.11 μM) 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.
Ključne reči:
Biginelli adduct / Azo-hydrazone tautomerism / Antitumor / Cell cycle arrest / ADMEIzvor:
Dyes and Pigments, 2021, 187, 109123-Izdavač:
- Elsevier
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200287 (Inovacioni centar Tehnološko-metalurškog fakulteta u Beogradu doo) (RS-200287)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200026 (Univerzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM) (RS-200026)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200135 (Univerzitet u Beogradu, Tehnološko-metalurški fakultet) (RS-200135)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200043 (Institut za onkologiju i radiologiju Srbije, Beograd) (RS-200043)
DOI: 10.1016/j.dyepig.2020.109123
ISSN: 0143-7208; 1873-3743
WoS: 000618738600003
Scopus: 2-s2.0-85098647658
Institucija/grupa
IHTMTY - JOUR AU - Tadić, Julijana D. AU - Lađarević, Jelena AU - Vitnik, Željko AU - Vitnik, Vesna AU - Stanojković, Tatjana AU - Matić, Ivana Z. AU - Mijin, Dušan PY - 2021 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/4172 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 μM) and PC-3 (48.98 μM) cancer cells, and normal MRC-5 (91.11 μM) 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. PB - Elsevier T2 - Dyes and Pigments T1 - Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity VL - 187 SP - 109123 DO - 10.1016/j.dyepig.2020.109123 ER -
@article{ author = "Tadić, Julijana D. and Lađarević, Jelena and Vitnik, Željko and Vitnik, Vesna and Stanojković, Tatjana and Matić, 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 μM) and PC-3 (48.98 μM) cancer cells, and normal MRC-5 (91.11 μM) 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.", publisher = "Elsevier", journal = "Dyes and Pigments", title = "Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity", volume = "187", pages = "109123", doi = "10.1016/j.dyepig.2020.109123" }
Tadić, J. D., Lađarević, J., Vitnik, Ž., Vitnik, V., Stanojković, T., Matić, I. Z.,& Mijin, D.. (2021). Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity. in Dyes and Pigments Elsevier., 187, 109123. https://doi.org/10.1016/j.dyepig.2020.109123
Tadić JD, Lađarević J, Vitnik Ž, Vitnik V, Stanojković T, Matić IZ, Mijin D. Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity. in Dyes and Pigments. 2021;187:109123. doi:10.1016/j.dyepig.2020.109123 .
Tadić, Julijana D., Lađarević, Jelena, Vitnik, Željko, Vitnik, Vesna, Stanojković, Tatjana, Matić, Ivana Z., Mijin, Dušan, "Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity" in Dyes and Pigments, 187 (2021):109123, https://doi.org/10.1016/j.dyepig.2020.109123 . .