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2030-01-01
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- IOC - Artigos de Periódicos [12973]
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IMATINIB DERIVATIVES AS INHIBITORS OF K562 CELLS IN CHRONIC MYELOID LEUKEMIA
Isatina
Inibidores da tirosina quinase
leucemia mielóide crônica
Imatinib
Sunitinib
Isatin
Phenylacetamide
chronic myeloid leukemia
Author
Affilliation
Abstract
Imatinib was the first representative of the class of
Breakpoint cluster region-Abelson murine leukemia viral
oncogene homolog (BCR-ABL) tyrosine kinase inhibitors
used for the treatment of chronic myeloid leukemia. Secondgeneration
and third-generation drugs have been introduced in
this therapy, affording increased patient survival. However, all
BCR-ABL tyrosine kinase inhibitors have been shown to
induce resistance, necessitating a search for new therapeutic
options. The sunitinib, another tyrosine kinase inhibitor used
in the treatment of renal cell carcinoma and gastrointestinal
stromal tumors is an isatin derivative. Isatin nucleus is highly
versatile for the preparation of new substances, and several
tyrosine kinase inhibitors examples have been obtained using
it. This work aimed to design, synthesize, and biological
evaluation of new compounds using the K562 cell line, which
constitutively expresses the active BCR-ABL enzyme. Three
new series of imatinib derivatives have been planned from the
imatinib, and all have a phenylaminopyrimidine group as the
main pharmacophore. Sunitinib was used as a structural
prototype to planning the series 1 (8a–e) of hybrids between
sunitinib and imatinib. Series 2 and 3 are 2-oxo-2-
phenyacetamide and 2,2-difluoro-2-phenylacetamide derivatives,
respectively. Isatins were used as the starting materials
for all series. Compounds were synthesized using simple
methodologies and were obtained in high purities. The compounds
were tested against K562 cells, and four showed a
reduction in cell viability, with EC50 values ranging from 0.37
to 2.02 μM, some of which are close to the imatinib standard
(0.21 μM).
Keywords in Portuguese
Mesilato de ImatinibIsatina
Inibidores da tirosina quinase
leucemia mielóide crônica
Keywords
Tyrosine kinase inhibitorsImatinib
Sunitinib
Isatin
Phenylacetamide
chronic myeloid leukemia
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