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Hybrids of Imatinib with Quinoline: Synthesis, Antimyeloproliferative Activity Evaluation, and Molecular Docking
| Content Provider | MDPI |
|---|---|
| Author | Santos, Carine Pimentel, Luiz Canzian, Henayle Oliveira, Andressa Junior, Floriano Dantas, Rafael Hoelz, Lucas Marinho, Debora Cunha, Anna Bastos, Monica Boechat, Nubia |
| Copyright Year | 2022 |
| Description | Imatinib (IMT) is the first-in-class BCR-ABL commercial tyrosine kinase inhibitor (TKI). However, the resistance and toxicity associated with the use of IMT highlight the importance of the search for new TKIs. In this context, heterocyclic systems, such as quinoline, which is present as a pharmacophore in the structure of the TKI inhibitor bosutinib (BST), have been widely applied. Thus, this work aimed to obtain new hybrids of imatinib containing quinoline moieties and evaluate them against K562 cells. The compounds were synthesized with a high purity degree. Among the produced molecules, the inhibitor 4-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)-N1-(quinolin-4-yl)benzene-1,3-diamine (2g) showed a suitable reduction in cell viability, with a $CC_{50}$ value of 0.9 µM (IMT, $CC_{50}$ = 0.08 µM). Molecular docking results suggest that the interaction between the most active inhibitor 2g and the BCR-ABL1 enzyme occurs at the bosutinib binding site through a competitive inhibition mechanism. Despite being less potent and selective than IMT, 2g is a suitable prototype for use in the search for new drugs against chronic myeloid leukemia (CML), especially in patients with acquired resistance to IMT. |
| Starting Page | 309 |
| e-ISSN | 14248247 |
| DOI | 10.3390/ph15030309 |
| Journal | Pharmaceuticals |
| Issue Number | 3 |
| Volume Number | 15 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-03-03 |
| Access Restriction | Open |
| Subject Keyword | Pharmaceuticals Medicinal Chemistry Cancer Imatinib Papp Quinoline 1,2,3-triazole Tyrosine Kinase Inhibitors |
| Content Type | Text |
| Resource Type | Article |
