quercetagetin and Neoplasms

Protein kinases have been important targets for antitumor targets due to their key roles in regulating multiple cell signaling pathways. Numerous compounds containing flavonoid scaffold as an indispensable anchor have been found to be potent inhibitors of protein kinases. Some of these flavonoids have been in clinical research as protein kinases inhibitors. Thus, the present review mainly focuses on the structural requirement for anticancer potential of flavone derivatives targeting several key serine/threonine protein kinases. This information may provide an opportunity to scientists of medicinal chemistry to design multi-functional flavone derivatives for the treatment of cancer.

Topics: Animals; Antineoplastic Agents; Flavones; Humans; Neoplasms; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases

c-Jun N-terminal kinases (JNKs), members of the mitogen-activated protein kinase (MAPK) family, are encoded by three genes:

Topics: Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Neoplasms; Phosphorylation; Protein Isoforms

The Pim protein kinases are frequently overexpressed in prostate cancer and certain forms of leukemia and lymphoma. 5-(3-Trifluoromethylbenzylidene)thiazolidine-2,4-dione (4a) was identified by screening to be a Pim-1 inhibitor and was found to attenuate the autophosphorylation of tagged Pim-1 in intact cells. Although 4a is a competitive inhibitor with respect to ATP, a screen of approximately 50 diverse protein kinases demonstrated that it has high selectivity for Pim kinases. Computational docking of 4a to Pim-1 provided a model for lead optimization, and a series of substituted thiazolidine-2,4-dione congeners was synthesized. The most potent new compounds exhibited IC(50)s of 13 nM for Pim-1 and 2.3 microM for Pim-2. Additional compounds in the series demonstrated selectivities of more than 2500-fold and 400-fold for Pim-1 or Pim-2, respectively, while other congeners were essentially equally potent toward the two isozymes. Overall, these compounds are new Pim kinase inhibitors that may provide leads to novel anticancer agents.

Topics: Animals; Antineoplastic Agents; Cell Line; Cell-Free System; Combinatorial Chemistry Techniques; Female; Humans; Kinetics; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Structure; Neoplasm Transplantation; Neoplasms; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-pim-1; Structure-Activity Relationship; Thiazolidinediones