Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions
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2022
Authors
Milović, EmilijaPetronijević, Jelena
Joksimović, Nenad
Beljkaš, Milan
Ružić, Dušan

Nikolić, Katarina

Vraneš, Milan
Tot, Aleksandar
Đorđić Crnogorac, Marija
Stanojković, Tatjana

Janković, Nenad

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Selected tetrahydropyrimidines (THPMs) were investigated by means of cytotoxic activities on selected cancer (HeLa, A549, and LS174) and non-cancerous cell lines (MRC-5). Among evaluated compounds, two of them ( B7 and B8 ) showed good cytotoxic activity on the tested cell lines and were selected for fur- ther evaluation that included mechanism of action, DNA and BSA interactions and molecular docking study. Calculated parameters from fluorescence quenching studies indicated that B7 and B8 bind on mi- nor groove of DNA and have great ability to bind on carrier protein. Three-dimensional quantitative struc- ture anti-HeLa activity study was performed with data set of THPMs. Molecular Interaction Fields were used to derive Grid independent descriptors (GRIND), as independent variables in Pentacle software. The quality and predictive capacity of the model was proved by internal statistical parameters: R 2 = 0.992, Q 2 = 0.51, as well as external parameters such as R 2 pred = 0.804 and r m... 2 , r / 2 m and r 2 m , that were higher than 0.5. The structural determinants significant for anti-HeLa activity of compounds were identified by using developed 3D-QSAR model. Interpretation of the most impactful GRIND variables on the anti-HeLa activity generated several hypotheses for design of novel and more potent anti-HeLa tetrahydropyrim- idines. Additional molecular targets for the most active synthesized derivatives ( B7 and B8 ) are predicted by use of online web-based tool-SwissTargetPrediction.
Source:
Journal of Molecular Structure, 2022, 1257Publisher:
- Elsevier B.V.
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200122 (University of Kragujevac, Faculty of Science) (RS-200122)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200378 (Institute of Information Technology) (RS-200378)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)
DOI: 10.1016/j.molstruc.2022.132621
ISSN: 0022-2860
WoS: 00078987780000
Scopus: 2-s2.0-85124650526
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Institution/Community
PharmacyMilović, E., Petronijević, J., Joksimović, N., Beljkaš, M., Ružić, D., Nikolić, K., Vraneš, M., Tot, A., Đorđić Crnogorac, M., Stanojković, T.,& Janković, N.. (2022). Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions. in Journal of Molecular Structure Elsevier B.V.., 1257. https://doi.org/10.1016/j.molstruc.2022.132621
Milović E, Petronijević J, Joksimović N, Beljkaš M, Ružić D, Nikolić K, Vraneš M, Tot A, Đorđić Crnogorac M, Stanojković T, Janković N. Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions. in Journal of Molecular Structure. 2022;1257. doi:10.1016/j.molstruc.2022.132621 .
Milović, Emilija, Petronijević, Jelena, Joksimović, Nenad, Beljkaš, Milan, Ružić, Dušan, Nikolić, Katarina, Vraneš, Milan, Tot, Aleksandar, Đorđić Crnogorac, Marija, Stanojković, Tatjana, Janković, Nenad, "Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions" in Journal of Molecular Structure, 1257 (2022), https://doi.org/10.1016/j.molstruc.2022.132621 . .