PMID- 36508971
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20230103
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 246
DP  - 2023 Jan 15
TI  - Novel thiazolidines of potential anti-proliferation properties against esophageal 
      squamous cell carcinoma via ERK pathway.
PG  - 114909
LID - S0223-5234(22)00811-X [pii]
LID - 10.1016/j.ejmech.2022.114909 [doi]
AB  - The discovery of a new class of extracellular-signal-regulated kinase (ERK) 
      inhibitors has been achieved via developing novel 
      2-imino-5-arylidene-thiazolidine analogues. A novel synthetic method employing a 
      solid support-mediated reaction was used to construct the targeted thiazolidines 
      through a cascade reaction with good yields. The chemical and physical stability 
      of the new thiazolidine library has successfully been achieved by blocking the 
      labile C5-position to aerobic oxidation. A cell viability study was performed 
      using esophageal squamous cell carcinoma cell lines (KYSE-30 and KYSE-150) and 
      non-tumorous esophageal epithelial cell lines (HET-1A and NES-G4T) through 
      utilization of an MTT assay, revealing that 
      (Z)-5-((Z)-4-bromobenzylidene)-N-(4-methoxy-2-nitrophenyl)-4,4-dimethylthiazolidin-2-imine 
      (6g) was the best compound among the synthesized library in terms of selectivity. 
      DAPI staining experiments were performed to visualize the morphological changes 
      and to investigate the apoptotic activity. Moreover, western blots were used to 
      probe the mechanism/pathway behind the observed activity/selectivity of 
      thiazolidine 6g which established selective inhibition of phosphorylation in the 
      ERK pathway. Molecular modeling techniques have been utilized to confirm the 
      observed activity. A molecular docking study revealed similar binding 
      interactions between the synthesized thiazolidines and reported co-crystalized 
      inhibitors with ERK proteins. Thus, the present study provides a starting point 
      for the development of interesting bioactive 2-imino-5-arylidene-thiazolidines.
CI  - Copyright (c) 2022 Elsevier Masson SAS. All rights reserved.
FAU - Aziz, Marian N
AU  - Aziz MN
AD  - Department of Chemistry and Biochemistry, 700 Planetarium Place, University of 
      Texas at Arlington, TX, 76019, USA; Department of Pesticide Chemistry, National 
      Research Centre, Dokki, Giza, 12622, Egypt.
FAU - Nguyen, Linh
AU  - Nguyen L
AD  - Dept. of Biology, College of Science, University of Texas at Arlington, TX, 
      76019, USA; Department of Graduate Nursing, College of Nursing and Health 
      Innovation, University of Texas at Arlington, TX, 76019, USA.
FAU - Chang, Yan
AU  - Chang Y
AD  - Department of Graduate Nursing, College of Nursing and Health Innovation, 
      University of Texas at Arlington, TX, 76019, USA; Bone and Muscle Research 
      Center, University of Texas at Arlington, TX, 76019, USA.
FAU - Gout, Delphine
AU  - Gout D
AD  - Department of Chemistry and Biochemistry, 700 Planetarium Place, University of 
      Texas at Arlington, TX, 76019, USA.
FAU - Pan, Zui
AU  - Pan Z
AD  - Department of Graduate Nursing, College of Nursing and Health Innovation, 
      University of Texas at Arlington, TX, 76019, USA; Bone and Muscle Research 
      Center, University of Texas at Arlington, TX, 76019, USA.
FAU - Lovely, Carl J
AU  - Lovely CJ
AD  - Department of Chemistry and Biochemistry, 700 Planetarium Place, University of 
      Texas at Arlington, TX, 76019, USA. Electronic address: lovely@uta.edu.
LA  - eng
PT  - Journal Article
DEP - 20221124
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - 0 (Thiazolidines)
SB  - IM
MH  - Humans
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - *Esophageal Squamous Cell Carcinoma/drug therapy
MH  - Thiazolidines/pharmacology/chemistry
MH  - *Esophageal Neoplasms/pathology
MH  - MAP Kinase Signaling System
MH  - Molecular Docking Simulation
MH  - Cell Line, Tumor
MH  - Cell Proliferation
COIS- Declaration of competing interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Carl J. Lovely reports financial support was provided by National 
      Science Foundation.
EDAT- 2022/12/13 06:00
MHDA- 2023/01/04 06:00
CRDT- 2022/12/12 18:25
PHST- 2022/07/15 00:00 [received]
PHST- 2022/11/02 00:00 [revised]
PHST- 2022/11/03 00:00 [accepted]
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2023/01/04 06:00 [medline]
PHST- 2022/12/12 18:25 [entrez]
AID - S0223-5234(22)00811-X [pii]
AID - 10.1016/j.ejmech.2022.114909 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2023 Jan 15;246:114909. doi: 10.1016/j.ejmech.2022.114909. Epub 
      2022 Nov 24.