- Design, synthesis and anticancer evaluation of thieno[2,3-d]pyrimidine derivatives as dual EGFR/HER2 inhibitors and apoptosis inducers
-
Deregulation of many kinases is directly linked to cancer development and the tyrosine kinase family is one of the most important targets in current cancer therapy regimens. In this study, we have designed and synthesized a series of thieno[2,3-d]pyrimidine derivatives as an EGFR and HER2 tyrosine kinase inhibitors. All the synthesized compounds were evaluated in vitro for their inhibitory activities against EGFRWT; and the most active compounds that showed promising IC50 values against EGFRWT were tested in vitro for their inhibitory activities against mutant EGFRT790M and HER2 kinases. Moreover, the antitumor activities of these compounds were tested against four cancer cell lines (HepG2, HCT-116, MCF-7 and A431). Compounds 13g, 13h and 13k exhibited the highest activities against the examined cell lines with IC50 values ranging from 7.592 ± 0.32 to 16.006 ± 0.58 μM comparable to that of erlotinib (IC50 ranging from 4.99 ± 0.09 to 13.914 ± 0.36 μM). Furthermore, the most potent antitumor agent (13k) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in MCF-7 cell line. The results indicated that this compound arrests G2/M phase of the cell cycle and it is a good apoptotic agent. Finally, molecular docking studies showed a good binding pattern of the synthesized compounds with the prospective target, EGFRWT and EGFRT790M.
- Elmetwally, Souad A.,Saied, Khaled F.,Eissa, Ibrahim H.,Elkaeed, Eslam B.
-
-
- Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin- 4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2
-
A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC 50 values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2.
- Golub, Andriy G.,Bdzhola, Volodymyr G.,Briukhovetska, Nadiia V.,Balanda, Anatoliy O.,Kukharenko, Olexander P.,Kotey, Igor M.,Ostrynska, Olga V.,Yarmoluk, Sergiy M.
-
p. 870 - 876
(2011/04/22)
-
- Synthesis, characterization and biological studies of some novel thieno[2,3-d]pyrimidines
-
Several 2-unsubstituted thieno[2,3-d]pyrimidines have been prepared from 2-aminothiophene-3-carboxylic acid esters and their carbonitrile analogs. Some triazolothienopyrimidine and 2-thioxothienopyrimidine representatives have also been synthesized using
- Al-Taisan, Khulud M.,Al-Hazimi, Hassan M. A.,Al-Shihry, Shar S.
-
experimental part
p. 3932 - 3957
(2010/09/18)
-
- Electrophilic cyanations. I. Synthesis of thiocyanato-heteroarenes and tosylheteroarenes from mercapto-heteroarenes using p-toluenesulfonyl cyanide
-
Mercaptoheteroarenes (1) underwent electrophilic cyanation with p-toluenesulfonyl cyanide (TsCN) in THF in the presence of NaH to give the corresponding thiocyanatoheteroarenes (2) in moderate to good yields. In DMF, tosylheteroarenes (4) were formed by substitution with p-toluenesulfinate ion through thiocyanatoheteroarenes (2).
- Miyashita, Akira,Nagasaki, Izuru,Kawano, Akiko,Suzuki, Yumiko,Iwamoto, Ken-Ichi,Higashino, Takeo
-
p. 745 - 755
(2007/10/03)
-