Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold.

Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold.

Publication date: May 15, 2019

In this work, a new series of imidazo[2,1-b]thiazole was designed and synthesized. The new compounds are having 3-fluorophenyl at position 6 of imidazo[2,1-b]thiazole and pyrimidine ring at position 5. The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. The final compounds were selected by NCI for in vitro cytotoxicity screening. Most derivatives showed cytotoxic activity against colon cancer and melanoma cell lines. In addition, ICs of the target compounds were determined over A375 and SK-MEL-28 cell lines using sorafenib as positive control. Compounds12b, 12c, 12e, 12f, 15a, 15d, 15f, 14g and 15h exhibited superior activity when compared to sorafenib. The most potent compounds were tested against wild type BRAF, v600e BRAF, and CRAF. Compound 15h exhibited a potential inhibitory effect againstBRAF (IC = 9.3 nM).

Abdel-Maksoud, Ammar, U.M., and Oh, C.H. Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazothiazole scaffold. 22605. 2019 Bioorg Med Chem (27):10.

Concepts Keywords
Amide Sorafenib
BRAF Pyrimidine
Colon V600E
Cytotoxic BRAF
Cytotoxicity Chloroarenes
Ethyl Melanoma
Linker Tyrosine kinase inhibitors
MEL Aromatic compounds
Melanoma Cancer treatments
Moiety Organic compounds
NCI Chemical compounds
Propyl
Pyrimidine
Ring
Sorafenib
Sulphonamide

Semantics

Type Source Name
gene UNIPROT BANF1
gene UNIPROT RAF1
drug DRUGBANK Sorafenib
gene UNIPROT RAB8A
pathway BSID Melanoma
disease MESH melanoma
disease DOID melanoma
disease DOID colon cancer
disease MESH colon cancer
gene UNIPROT BRAF

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