22476-62-6Relevant academic research and scientific papers
Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells
Zhou, Hongyu,Wu, Shuhong,Zhai, Shumei,Liu, Aifeng,Sun, Ying,Li, Rongshi,Zhang, Ying,Ekins, Sean,Swaan, Peter W.,Fang, Bingliang,Zhang, Bin,Yan, Bing
, p. 1242 - 1251 (2008/12/23)
Ten cytoselective compounds have been identified from 372 thiazolidinone analogues by applying iterative library approaches. These compounds selectively killed both non-small cell lung cancer cell line H460 and its paclitaxel-resistant variant H460taxR at an IC50 between 0.21 and 2.93 μM while showing much less toxicity to normal human fibroblasts at concentrations up to 195 μM. Structure-activity relationship studies revealed that (1) the nitrogen atom on the 4-thiazolidinone ring (ring B in Figure 1) cannot be substituted, (2) several substitutions on ring A are tolerated at various positions, and (3) the substitution on ring C is restricted to the -NMe2 group at the 4-position. A pharmacophore derived from active molecules suggested that two hydrogen bond acceptors and three hydrophobic regions were common features. Activities against P-gp-overexpressing and paclitaxel-resistant cell line H460taxR and modeling using a previously validated P-gp substrate pharmacophore suggested that active compounds were not likely P-gp substrates.
[4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A novel class of highly potent colchicine site binding tubulin inhibitors: Synthesis and cytotoxic activity on selected human cancer cell lines
Mahboobi, Siavosh,Sellmer, Andreas,H?cher, Heymo,Eichhorn, Emerich,B?r, Thomas,Schmidt, Mathias,Maier, Thomas,Stadlwieser, Josef F.,Beckers, Thomas L.
, p. 5769 - 5776 (2007/10/03)
Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]-phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27kip1 and the influence on microtubule formation were investigated. Considering the significant correlation between the IC50 values of tubulin polymerization inhibition, [3H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin. In depth analysis of the investigated compounds allowed the identification of modifications that altered the pharmacological profile of the compounds from a mitosis-inducing phenotype to a G1 cell cycle arresting phenotype.
