81021-96-7Relevant articles and documents
Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors
Shaik, Siddiq Pasha,Vishnuvardhan,Sultana, Faria,Subba Rao,Bagul, Chandrakant,Bhattacharjee, Debanjan,Kapure, Jeevak Sopanrao,Jain, Nishant,Kamal, Ahmed
, p. 3285 - 3297 (2017/05/29)
1,2,3-Triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates (5a–v) were designed, synthesized and evaluated for their cytotoxic potency against some human cancer cell lines like DU-145 (prostate), HeLa (cervical), MCF-7 (breast) HepG2 (liver) and A549 (lung). Preliminary results revealed that some of these conjugates like 5f and 5k exhibited significant antiproliferative effect against human breast cancer cells (MCF-7) with IC50 values of 0.60 and 0.78?μM respectively. Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G2/M phase which was further authenticated by elevation of cyclin B1 protein levels. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 5f and 5k, and western blot analysis revealed that these conjugates accumulated more tubulin in the soluble fraction. Moreover, the conjugates caused apoptosis of the cells that was confirmed by mitochondrial membrane potential and Annexin V-FITC assay. Molecular docking studies indicated that these conjugates occupy the colchicine binding site of the tubulin protein.
Discovery of imidazo[2,1- b ]thiazole HCV NS4B inhibitors exhibiting synergistic effect with other direct-acting antiviral agents
Wang, Ning-Yu,Xu, Ying,Zuo, Wei-Qiong,Xiao, Kun-Jie,Liu, Li,Zeng, Xiu-Xiu,You, Xin-Yu,Zhang, Li-Dan,Gao, Chao,Liu, Zhi-Hao,Ye, Ting-Hong,Xia, Yong,Xiong, Ying,Song, Xue-Jiao,Lei, Qian,Peng, Cui-Ting,Tang, Hong,Yang, Sheng-Yong,Wei, Yu-Quan,Yu, Luo-Ting
, p. 2764 - 2778 (2015/04/14)
The design, synthesis, and SAR studies of novel inhibitors of HCV NS4B based on the imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (EC50 = 16
Structure-activity relationship of 6-methylidene penems bearing tricyclic heterocycles as broad-spectrum β-lactamase inhibitors: Crystallographic structures show unexpected binding of 1,4-thiazepine intermediates
Venkatesan, Aranapakam M.,Gu, Yansong,Santos, Osvaldo Dos,Abe, Takao,Agarwal, Atul,Yang, Youjun,Petersen, Peter J.,Weiss, William J.,Mansour, Tarek S.,Nukaga, Michiyoshi,Hujer, Andrea M.,Bonomo, Robert A.,Knox, James R.
, p. 6556 - 6568 (2007/10/03)
The design and synthesis of a series of seven tricyclic 6-methylidene penems as novel class A and C serine β-lactamase inhibitors is described. These compounds proved to be very potent inhibitors of the TEM-1 and AmpC β-lactamases and less so against the class B metallo-β-lactamase CcrA. In combination with piperacillin, their in vitro activities enhanced susceptibility of all class C resistant strains from various bacteria. Crystallographic structures of a serine-bound reaction intermediate of 17 with the class A SHV-1 and class C GC1 enzymes have been established to resolutions of 2.0 and 1.4 A?, respectively, and refined to R-factors equal 0.163 and 0.145. In both β-lactamases, a seven-membered 1,4-thiazepine ring has formed. The stereogenic C7 atom in the ring has the R configuration in the SHV-1 intermediate and has both R and S configurations in the GC1 intermediate. Hydrophobic stacking interactions between the tricyclic C7 substituent and a tyrosine side chain, rather than electrostatic or hydrogen bonding by the C3 carboxylic acid group, dominate in both complexes. The formation of the 1,4- thiazepine ring structures is proposed based on a 7-endo-trig cyclization.
