New Approaches for the Synthesis of 2,3,5,6-Tetrahydrobenzo[d]thiazole Derivatives and their Anti- proliferative , c-Met Enzymatic Activity and Tyrosine Kinases Inhibitions

Background: Many tetrahydrobenzo[d]thiazole derivatives were considered as the most important class of heterocyclic compounds due to their biological applications. There are many drugs known in the market containing the thiazole moiety which is responsible for the high drug activity.

Objective: This work aimed to produce novel heterocyclic compounds such as pyrazole, isoxazole, thiophene, chromeno[7,8-d]thiazole, and thiazolo[4,5-h]quinoline derivatives. The newly synthesized heterocyclic compounds were evaluated against anticancer cell lines followed by c-Met enzymatic activity and tyrosine kinases inhibition for the most active compounds.

Methods: In this work, the 3-phenyl-2-thioxo-2,3,5,6-tetrahydrobenzo[d]thiazol-7(4H)-one (3) was synthesized through the reaction of cyclohexane-1,3-dione with phenyl isothiocyanate and elemental sulfur. Compound 3 showed interesting activity toward some chemical reagents producing new heterocyclic compounds that can't be obtained through another way. The newly synthesized compounds were evaluated towards the six cancer cell lines. The most active compounds were selected and tested toward c-Met enzyme by taking foretinib as the positive control. Also, the inhibitions toward the PC-3 cell line using the reference SGI-1776 were measured. Finally, the inhibitions towards the five tyrosine kinases were also tested.

Results: The synthesized quinoline and chromene derivatives were evaluated toward c-Met enzyme using foretinib as the positive control the obtained results showed that twelve compounds exhibited IC50 values less than 1.30 nM. On the other hand, sixteen compounds showed higher inhibitions than the reference SGI-1776 (IC50 4.86 nM) toward the PC-3 cell line.

Conclusion: Novel, heterocyclic compounds were synthesized with a high impact of biological activities. All synthesized compounds were screened for their anti-proliferative effect and most of them revealed high potent effects. In addition, the c-Met and prostate cancer cell line PC-3 inhibitions for the most active compounds showed that these compounds exhibited high inhibitions. Anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions.

Related Products

Cat.No.	Product Name	Information
S1111	Foretinib	Foretinib is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met (c-Met) and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2.

Related Targets

c-Kit PDGFR VEGFR c-Met FLT3