69502-33-6Relevant articles and documents
A synthetic 2,3-diarylindole induces microtubule destabilization and G2/M cell cycle arrest in lung cancer cells
Thanaussavadate, Bongkotrat,Ngiwsara, Lukana,Lirdprapamongkol, Kriengsak,Svasti, Jisnuson,Chuawong, Pitak
, (2019/11/14)
The anticancer potential of a synthetic 2,3-diarylindole (PCNT13) has been demonstrated in A549 lung cancer cells by inducing both apoptosis and autophagic cell death. In this report, we designed to connect a fluorophore to the compound via a hydrophilic linker for monitoring intracellular localization. The best position for linker attachment was identified from cytotoxicity and effect on cell morphology of newly synthesized PCNT13 derivatives bearing hydrophilic linker. Cytotoxicity and effect on cell morphology related to the parental compound were used to identify the optimum position for linker attachment in the PCNT13 chemical structure. The fluorophore-PCNT13 conjugate was found to localize in the cytoplasm. Microtubules were found to be one of the cytosolic target proteins of PCNT13, as the compound could inhibit tubulin polymerization in vitro. A molecular docking study revealed that PCNT13 binds at the colchicine binding site on the α/β-tubulin heterodimer. The effect of PCNT13 on microtubule dynamics caused cell cycle arrest in the G2/M phase as analyzed by flow cytometric analysis.
MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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Paragraph 001481-001482, (2019/10/29)
The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
Preparation of 7-methoxy tacrine dimer analogs and their in vitro/in silico evaluation as potential cholinesterase inhibitors
Lee, Sang Kwang,Park, Min Kyun,Jhang, Ho Eun,Yi, Jinju,Nahm, Keepyong,Cho, Dae Won,Ra, Choon Sup,Musilek, Kamil,Horova, Anna,Korabecny, Jan,Dolezal, Rafael,Jun, Daniel,Kuca, Kamil Kuca
, p. 1654 - 1660 (2015/07/15)
Novel types of symmetric bis-7-methoxytacrines connected by oligoethyleneoxy chains 3-5 and nonsymmetric monomeric 7-methoxytacrines containing hydroxyl-terminated oligoethyleneoxy chains 6-8 were prepared, and their in vitro/in silico effects on human recombinant AChE (hAChE) and human plasmatic butyrylcholinesterase (hBChE) were compared, with 7-MEOTA (2) as the standard compound. The symmetric bis-7-MEOTA derivatives 3-5 showed hAChE inhibition similar to that of 2. On the other hand, their effects on hBChE revealed an increasing inhibition trend when the oligoethyleneoxy units between the two 7-MEOTA moieties became longer. Accordingly, compounds 4 and 5 showed better selectivity towards hBChE. The most effective in the inhibition hAChE and hBChE was compound 8 with the longest oligoethyleneglycol chain, whereas compounds 6 and 7 resulted in similar IC50 values. A molecular modeling study using substrates 5 and 8 showed a possible binding conformation and protein-ligand interaction between the substrates and AChE/BChE.
