Protein-tyrosine kinase inhibitory

CUSHMAN M, NAGARATHMAN D, BURG D L and GEAHLEN R L (1991) Synthesis and protein-tyrosine kinase inhibitory activity of flavonoids analogues Journal cjf Medicinal Chemistry 34, 798-806. 

Representatives of the l-benzylidene-[l,4]oxazino[3,4- ]quinazolin-6-ones prepared from 315 exhibit remarkable protein-tyrosine kinase inhibitory activity and inhibit the growth of tumor cells <1996BMC547, 2001USP6331555, 2002BBA318>. 

A simple procedure to prepare 5-aryl- and 5-pyridyl-2-furaldehydes from inexpensive, commercially available 2-furaldehyde diethyl acetal was reported. The reaction proceeded in a four-step, one-pot procedure and the yield of coupling step was usually between 58-91% <02OL375>. A facile route to 3,4-furandicarboxylic acids was developed. DDQ-oxidation of 2,5-dihydrofuran derivatives, which were produced from dimethyl maleic anhydride, furnished the desired esters of furan-3,4-dicarboxylic acid <02S1010>. The furan-fused tetracyclic core of halenaquinol and halenaquinone possessing antibiotic, cardiotonic, and protein tyrosine kinase inhibitory activities was synthesized. Intramolecular cycloaddition of an o-quinodimethane with furan gave the adduct as a single isomer via an enrfo-transition state, which was converted to trisubstituted furan by oxidation-elimination reactions <02T6097>. 

Thakkar, K., Geahlen, R.L. and Cushman, M. (1993) Synthesis and protein-tyrosine kinase inhibitory activity of polyhydroxylated stilbene analogues of piceatarmol. J. Med. Chem. 36 2950-2955. 

ShibasaM and coworkers [117] described the first enantioselective combination of this type in their synthesis of the natural product halenaquinone (225) possessing antibiotic, cardiotonic and protein tyrosine kinase inhibitory activities. The key step is an intermolecular Suzuki reaction of 222 and 223 followed by an enantioselective Mizoroki-Heck reaction in the presence of (5 )-BINAP to construct the third ring and the stereogenic quaternary centre present in 224. The reaction proceeded with a good cc-value of 85% but with a yield of only 20% (Scheme 8.56). 

Cushman M, Nagarathnam D, Burg DL et al (1991) Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid analogues. J Med Chem 34 798-806... 

Hollosy F, Meszaros G, Bokonyi G et al (2000) Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in human tumor cells. Anticancer Res 20 4563-4570 Honda NK, Pavan FR, Coelho RG et al (2010) Antimycobacterial activity of lichen substances. 

QSAR of protein tyrosine kinase inhibitory activity of fiavonoid anaiogues... 

Deeb, O. and Clare, B.W., (2007). QSAR of Aromatic Substances Protein Tyrosine Kinase Inhibitory Activity of Flavonoid Analogues. Chem. Biol Drug. Des., 70,437-449. 

Halenaquinone and Halenaquinol have been isolated from a variety of sea sponges and have been shown to possess antibiotic, cardiotonic and protein tyrosine kinase inhibitory activity [37]. Kojima et al. have employed a number of novel palladium-catalyzed cascade reactions in the total synthesis of Halenaquinone and Halenaquinol (Scheme 7.18) [38]. First, P-alkyl Suzuki-Miyaura Coupling/... 

Melemeleones A and B (320 and 321) possess a 4,9-friedodrimane sesquiterpene array linked to a quinone bearing a taurine and they are structurally related to avarol. Compounds 320 and 321 were isolated from the sponge Dysidea sp. and identified by analysis of their spectroscopic data. Compound 321 showed a moderate inhibitory activity against the pp60v src protein Tyrosine Kinase with an IC50 of 28 pM [236]. 

A Chinese isolate of Penicillium terrestre derived from sediments yielded a series of new gentisyl alcohol polymers, including the trimeric terrestriol A (89) and the dimeric terrestrols B-H (90-96)/° All compounds showed moderate cytotoxicity toward four different cancer cell lines as well as moderate radical scavenging activity in the DPPH assay. Furthermore, 95 displayed moderate inhibitory activity against protein tyrosine kinases Src and KDR. 

Figure 21-14 illustrates the functions of four proteins that regulate the protein kinase activity of the 5. pombe CDK. First is Cdcl3, the mitotic cyclin of S. pombe (equivalent to cyclin B in metazoans), which associates with the CDK to form MPF with extremely low activity. Second is the Weel protein-tyrosine kinase, which phosphorylates an inhibitory tyrosine residue (Y15) in the CDK subunit. Third is another kinase, designated CDK-activating kinase (CAK), which phosphorylates an activating threonine residue (T161). When... 

The current preferred postulated mechanism of vanadium s in vitro effects is that vanadate stimulates specific protein-tyrosine phosphorylation by virtue of its inhibitory actions on appropriate PTPases. Routine addition of vanadate to cell lysates, particularly for tyrosine kinase assays, is testimony of the ability of vanadate to preserve the phosphotyrosine content of cells. The preponderance of evidence favors a post-receptor mechanism in stimulating glucose utilization, perhaps also involving a cytosolic i.e. non-receptor) protein tyrosine kinase that is stimulated preferentially by vanadium and may be insulin independent. Vanadyl is not a potent PTPase inhibitor. " Thus, whatever portion of intracellular vanadium is present as vanadyl is probably acting by some alternative mechanism. ... 

In opposition, leukemias of the New Word monkeys (marmosets, tamarins) are caused by herpesviruses. The reticuloendothelial virus sequence-carrier Marek s avian (turkeys) herpesvirus represents a unique unison of the two viral taxa reviewed in [27]. The genome of the gammaherpesvirus of squirrel monkeys (Saimiri sciureus), Herpesvirus saimiri, operates from its epigenomic position by emitting small RNAs inhibitory to host cell mRNAs. The H. saimiri genomic tip-484 (tyrosine kinase interacting protein) constitutively activates host ceU Lck (Src family member lymphocyte-specific p56 protein tyrosine kinase) and STAT to... 

A different mode of interference of ascorbate with growth factor receptors was suggested by Monteiro et al. (1993). In HER 14 cells, physiological concentrations of ascorbate inhibited a protein tyrosine phosphatase acting on the EGF receptor. The effect could be prevented by EGF. Interestingly, the inhibitory effect of ascorbate on the phosphatase was more pronounced at low concentrations of ascorbate and low cell density, which was interpreted by the authors as indicating a prooxidant action of ascorbate. Activation of signal transduction pathways has been described for the insulin receptor tyrosine kinase (Koshio et al., 1988) and a protein tyrosine kinase in the rat liver plasma membrane (Chan et al., 1986). 

A potential imderlying mechanism may be related to the isoflavone content of soy proteins. It has been shown that soy may play an inhibitory role in protein synthesis in vitro and in animal models.It has been shown that the isoflavones present in varying concentrations in soy products are cytotoxic in vitro, partially due to their inhibition of protein tyrosine kinase and DNA topoisomerase activities. However, these mechanisms have not been elucidated in humans. The amount of soy isoflavones in the soy proteins administered or present in the blood have not been widely presented in these studies assessing PS. 

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