Home About us Contact
|
Home About us Contact | ||
|
|
||
Potent Antitumor Agent (potent + antitumor_agent)
Selected AbstractsCharacterization of the Interaction of TZT-1027, a Potent Antitumor Agent, with TubulinCANCER SCIENCE, Issue 7 2000Tsugitaka Natsume TZT-1027, a derivative of dolastatin 10 isolated from the Indian Ocean sea hare Dolabella auricularia in 1987 by Pettit et al., is a potent antimicrotubule agent. We have compared the activity of TZT-1027 with that of dolastatin 10 as well as the vinca alkaloids vinblastine (VLB), vincristine (VCR) and vindesine (VDS). TZT-1027 and dolastatin 10 inhibited microtubule polymerization concentration-dependently at 1,100 ,M with IC50 values of 2.2±0.6 and 2.3±0.7 ,M, respectively. VLB, VCR and VDS inhibited microtubule polymerization at 1,3 ,M with IC50 values of 2.7±0.6, 1.6±0.4 and 1.6±0.2 ,M, respectively, but showed a slight decrease in inhibitory effect at concentrations of 10 ,M or more. TZT-1027 also inhibited monosodium glutamate-induced tubulin polymerization concentration-dependently at 0.3,10 ,M, with an IC50 of 1.2 ,M, whereas VLB was only effective at 0.3,3 ,M, with an IC50 of 0.6 ,M, and caused so-called "aggregation" of tubulin at 10 ,M. Scatchard analysis of the binding data for [3H]VLB suggested one binding site (Kd 0.2±0.04 ,M and Bmax 6.0±0.26 nM/mg protein), while that for [3H]TZT-1027 suggested two binding sites, one of high affinity (Kd 0.2±0.01 ,M and Bmax 1.7±0.012 nM/mg protein) and the other of low affinity (Kd 10.3±1.46 ,M, and Bmax 11.6±0.83 nM/mg protein). [3H]TZT-1027 was completely displaced by dolastatin 10 but only incompletely by VLB. [3H]VLB was completely displaced by dolastatin 10 and TZT-1027. Furthermore, TZT-1027 prevented [3H]VLB from binding to tubulin in a non-competitive manner according to Lineweaver-Burk analysis. TZT-1027 concentrationdependently inhibited both [3H]guanosine 5,-triphosphate (GTP) binding to and GTP hydrolysis on tubulin. VLB inhibited the hydrolysis of GTP on tubulin concentration-dependently to a lesser extent than TZT-1027, but no inhibitory effect of VLB on [3H]GTP binding to tubulin was evident even at 100 ,M. Thus, TZT-1027 affected the binding of VLB to tubulin, but its binding site was not completely identical to that of VLB. TZT-1027 had a potent inhibitory effect on tubulin polymerization and differed from vinca alkaloids in its mode of action against tubulin polymerization. [source] ChemInform Abstract: 2-[N1 -2-Pyrimidyl-aminobenzenesulfonamido] Ethyl 4-Bis(2-chloroethyl) Aminophenyl Butyrate: A Potent Antitumor Agent.CHEMINFORM, Issue 32 2001Zhaohua Huang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Total Synthesis of Potent Antitumor Agent (,)-Lasonolide,A: A Cycloaddition-Based StrategyCHEMISTRY - AN ASIAN JOURNAL, Issue 10 2008Abstract A detailed account of the enantioselective total synthesis of (,)-lasonolide,A is described. Our initial synthetic route to the top tetrahydropyran ring involved Evans asymmetric alkylation as the key step. Initially, we relied on the diastereoselective alkylation of an ,-alkoxyacetimide derivative containing an ,, stereogenic center and investigated such an asymmetric alkylation reaction. Although alkylation proceeded in good yield, the lack of diastereoselectivity prompted us to explore alternative routes. Our subsequent successful synthetic strategies involved highly diastereoselective cycloaddition routes to both tetrahydropyran rings of lasonolide,A. The top tetrahydropyran ring was constructed stereoselectively by an intramolecular 1,3-dipolar cycloaddition reaction. The overall process constructed a bicyclic isoxazoline, which was later unravelled to a functionalized tetrahydropyran ring as well as a quaternary stereocenter present in the molecule. The lower tetrahydropyran ring was assembled by a Jacobsen catalytic asymmetric hetero-Diels,Alder reaction as the key step. The synthesis also features a Lewis acid catalyzed epoxide opening to form a substituted ether stereoselectively. [source] Synthesis and Evaluation of 3-Methyl-4-oxo-6-phenyl-4,5,6,7-tetrahydrobenzofuran-2-carboxylic Acid Ethyl Ester Derivatives as Potent Antitumor Agents.CHEMINFORM, Issue 48 2005Ichiro Hayakawa Abstract For Abstract see ChemInform Abstract in Full Text. [source] | ||||||||||