Design, Synthesis, Cytoselective Toxicity, Structure–Activity Relationships, and Pharmacophore of Thiazolidinone Derivatives Targeting Drug-Resistant Lung Cancer Cells

2008 ◽  
Vol 51 (5) ◽  
pp. 1242-1251 ◽  
Author(s):  
Hongyu Zhou ◽  
Shuhong Wu ◽  
Shumei Zhai ◽  
Aifeng Liu ◽  
Ying Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Drug Resistant ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals Structure–Activity Relationships and Molecular Docking Analysis of Mcl-1 Targeting Renieramycin T Analogues in Patient-derived Lung Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 875 ◽  
Author(s):  
Korrakod Petsri ◽  
Masashi Yokoya ◽  
Sucharat Tungsukruthai ◽  
Thanyada Rungrotmongkol ◽  
Bodee Nutho ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Benzene Ring ◽  
Lung Cancer Cells ◽  
Docking Analysis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Anti Cancer ◽  
Molecular Docking Analysis

Myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins are promising targets for cancer therapy. Here, we investigated the structure–activity relationships (SARs) and performed molecular docking analysis of renieramycin T (RT) and its analogues and identified the critical functional groups of Mcl-1 targeting. RT have a potent anti-cancer activity against several lung cancer cells and drug-resistant primary cancer cells. RT mediated apoptosis through Mcl-1 suppression and it also reduced the level of Bcl-2 in primary cells. For SAR study, five analogues of RT were synthesized and tested for their anti-cancer and Mcl-1- and Bcl-2-targeting effects. Only two of them (TM-(–)-18 and TM-(–)-4a) exerted anti-cancer activities with the loss of Mcl-1 and partly reduced Bcl-2, while the other analogues had no such effects. Specific cyanide and benzene ring parts of RT’s structure were identified to be critical for its Mcl-1-targeting activity. Computational molecular docking indicated that RT, TM-(–)-18, and TM-(–)-4a bound to Mcl-1 with high affinity, whereas TM-(–)-45, a compound with a benzene ring but no cyanide for comparison, showed the lowest binding affinity. As Mcl-1 helps cancer cells evading apoptosis, these data encourage further development of RT compounds as well as the design of novel drugs for treating Mcl-1-driven cancers.

Abstract 953: JARID1 family inhibitor reduces generation of drug-resistant EGFR mutation-positive lung cancer cells

2019 ◽  
Author(s):  
Shin Ariga ◽  
Ichiro Kinoshita ◽  
Junko Kikuchi ◽  
Yasushi Shimizu ◽  
Hirotoshi Dosaka-Akita
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Egfr Mutation ◽  
Lung Cancer Cells ◽  
Drug Resistant
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