Background:
Benzo[d]imidazoles are highly biologically active, in addition, they are considered as a class of heterocyclic
compounds with many pharmaceutical applications.
Objective:
We are aiming in this work to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. The
target molecules were obtained starting from the benzo[d]imidazole derivatives followed by their heterocyclization reactions to produce
anticancer target molecules.
Methods:
The 1-(1H-benzo[d]imidazol-2-yl)propan-2-one (3) and the ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate (16) were used as the
key starting material which reacted with salicylaldehyde to give the corresponding benzo[4,5]imidazo[1,2-a]quinoline derivatives. On
the other hand, both of them were reacted with different reagents to give thiophene, pyran and benzo[4,5]imidazo[1,2-c]pyrimidine
derivatives. The synthesized compounds were evaluated against the six cancer cell lines A549, HT-29, MKN-45, U87MG, and SMMC7721 and H460 together with inhibitions toward tyrosine kinases, c-Met kinase and prostate cancer cell line PC-3 were recorded using the
standard MTT assay in vitro, with foretinib as the positive control.
Results:
Most of the synthesized compounds exhibited high inhibitions toward the tested cancer cell lines. In addition, tyrosine and Pim1 kinases inhibitions were performed for the most active compounds where variation of substituent through the aryl ring and heterocyclic
ring afforded compounds with high activities. Our analysis showed that there is a strong correlation between structure of compound and
substituents of target molecules.
Conclusion:
Our present research proved that the synthesized heterocyclic compounds with varieties of substituents has a strong impact
through the activity of compounds. The evaluations through different cell lines and tyrosine kinases indicated that the compounds were
excellent candidates as anticancer agents. This could encourage doing further research within this field for the building of compounds
with high inhibitions.
Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents
