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Synthesis of new 2-aminothiazolyl/benzothiazolyl-based 3,4-dihydropyrimidinones and evaluation of their effects on adenocarcinoma gastric cell migration

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Abstract

Gastric cancer is one of the malignant tumors of the gastrointestinal tract that, despite its decrease in recent years, is still the fourth most common cancer and the second leading cause of cancer-related death. Various strategies including chemotherapy are used to keep cancer cells from spreading and induce apoptotic death in them. Recent studies have shown that dihydropyrimidinones (DHPMs) are privileged structures in medicinal chemistry due to their pharmacological effects. A number of new 2-aminothiazolyl/benzothiazolyl derivatives of 3,4-DHPMs (3–8) were synthesized and structurally identified, and then their effects on the migration behavior of human AGS cells (gastric cancer cells) were investigated. Molecular docking and molecular dynamics (MD) simulations were applied to explore binding potential and realistic binding model of the assessed derivatives through identification of key amino acid residues within L5/α2/α3 allosteric site of kinesin 5 (Eg5) as a validated microtubule-dependent target for monastrol as a privileged DHPM derivative.

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Acknowledgements

The research leading to offered results received funding from Ardabil University of Medical Sciences (ARUMS) under Grant No. IR.ARUMS.REC.1398.259.

Funding

The research leading to offered results received funding from Ardabil University of Medical Sciences (ARUMS) under Grant No. IR.ARUMS.REC.1397.137.

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Authors and Affiliations

  1. Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

    Mohsen Sagha

  2. Student Research Committee, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

    Fatemeh Mousaei & Mahtab Salahi

  3. Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 5618953141, Ardabil, Iran

    Nima Razzaghi-Asl

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  1. Mohsen Sagha
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  2. Fatemeh Mousaei
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  4. Nima Razzaghi-Asl
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All authors contributed equally in this work (concept, design, definition of intellectual content, literature search, experimental studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing and manuscript review).

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Correspondence to Nima Razzaghi-Asl.

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Sagha, M., Mousaei, F., Salahi, M. et al. Synthesis of new 2-aminothiazolyl/benzothiazolyl-based 3,4-dihydropyrimidinones and evaluation of their effects on adenocarcinoma gastric cell migration. Mol Divers 26, 1039–1051 (2022). https://doi.org/10.1007/s11030-021-10229-z

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  • DOI: https://doi.org/10.1007/s11030-021-10229-z

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