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New thiazolopyrimidine as anticancer agents: Synthesis, biological evaluation, DNA binding, molecular modeling and ADMET study.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Dec 01; Vol. 30 (23), pp. 127611. Date of Electronic Publication: 2020 Oct 14. - Publication Year :
- 2020
-
Abstract
- In the present study, new series of thiazolopyrimidine derivatives was synthesized as purine analogs. The structures of the products were confirmed through spectroscopic techniques such as NMR and mass spectrometry. In addition, the synthesized compounds were evaluated as antitumor active agent through NCI screening protocol against 60 different cell lines under 9 different panels. Furthermore, DNA binding activity of the compounds was also evaluated. The results revealed that compound 35 proved to be the most active member of the tested series and it is promoted to the 5-dose testing where it gives GI <subscript>50</subscript> , TGI and LC <subscript>50</subscript> values of 1.07, 6.61, 34.7 μM respectively. Furthermore, it also proved to have a good DNA binding activity with value that is comparable with that produced by doxorubicin which was used as positive standard. In addition, compound 27 was proved to be the most active DNA binding agent with binding affinity 28.38 ± 1.1. The pharmacokinetic properties were also calculated. Molecular docking studies suggested binding mode of compounds 27 and 35 to DNA minor groove via hydrogen bonding interaction. The anticancer activity of compounds 27 and 35 may be attributed to DNA binding.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents metabolism
Antineoplastic Agents pharmacokinetics
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Hydrogen Bonding
Molecular Docking Simulation
Pyrimidines chemical synthesis
Pyrimidines metabolism
Pyrimidines pharmacokinetics
Thiazoles chemical synthesis
Thiazoles metabolism
Thiazoles pharmacokinetics
Antineoplastic Agents pharmacology
DNA metabolism
Pyrimidines pharmacology
Thiazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 30
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 33068712
- Full Text :
- https://doi.org/10.1016/j.bmcl.2020.127611