23051-16-3Relevant articles and documents
Synthesis and antitumor evaluation of 5-(benzo[: D] [1,3]dioxol-5-ylmethyl)-4-(tert -butyl)- N -arylthiazol-2-amines
Wu,Fang,Tang,Xiao,Ye,Li,Hu
, p. 1768 - 1774 (2016/09/28)
A series of novel N-aryl-5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)thiazol-2-amines (C1-C31) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent.
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.
Hydrogen bond controlled aggregation of guanidinium-carboxylate derivatives in the solid state
Zafar, Abdullah,Melendez, Rosa,Geib, Steven J,Hamilton, Andrew D
, p. 683 - 690 (2007/10/03)
In this paper, we report the synthesis and aggregation properties of new self-complementary organic molecules containing guanidinium and carboxylate groups. The crystal structures of the guanidinium carboxylates showed linear bidentate hydrogen bonding between the guanidinium and the carboxylate groups. In the case of phenyl derivative 7, steric factors force a non-planar geometry for the hydrogen bonding subunit. Substitution of the phenyl by a pyridine leads to the formation of an intramolecular hydrogen bond and a planar conformation for the subunit. As a result, the simple intramolecularly hydrogen bonded molecule maintains a rigid control of binding group disposition in a manner similar to more complex multiple fused ring systems.
Substituted N-phenylisothioureas: Potent inhibitors of human nitric oxide synthase with neuronal isoform selectivity
Shearer, Barry G.,Lee, Shuliang,Oplinger, Jeffrey A.,Frick, Lloyd W.,Garvey, Edward P.,Furfine, Eric S.
, p. 1901 - 1905 (2007/10/03)
S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both the human constitutive and inducible isoforms of nitric oxide synthase. A series of substituted N-phenylisothiourea analogues was synthesized to investigate the structure-activity relationship of this class of inhibitor. Each analogue was evaluated for human isoform selectivity. One analogue, S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold selectivity for the neuronal isoform versus the inducible and endothelial derived constitutive isoforms, respectively. Studies have shown the substituted N-phenylisothiourea 39 binds competitively with L,-arginine.
