scholarly journals Design and Synthesis of Water-Soluble and Potent MMP-13 Inhibitors with Activity in Human Osteosarcoma Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 9976
Author(s):  
Jose Maria Zapico ◽  
Lourdes Acosta ◽  
Miryam Pastor ◽  
Loganathan Rangasamy ◽  
Laura Marquez-Cantudo ◽  
...  

Osteoarthritis is a degenerative disease, often resulting in chronic joint pain and commonly affecting elderly people. Current treatments with anti-inflammatory drugs are palliative, making the discovery of new treatments necessary. The inhibition of matrix metalloproteinase MMP-13 is a validated strategy to prevent the progression of this common joint disorder. We recently described polybrominated benzotriazole derivatives with nanomolar inhibitory activity and a promising selectivity profile against this collagenase. In this work, we have extended the study in order to explore the influence of bromine atoms and the nature of the S1′ heterocyclic interacting moiety on the solubility/selectivity balance of this type of compound. Drug target interactions have been assessed through a combination of molecular modeling studies and NMR experiments. Compound 9a has been identified as a water-soluble and highly potent inhibitor with activity in MG-63 human osteosarcoma cells.

2016 ◽  
Author(s):  
Jose M Moran ◽  
Olga Leal-Hernandez ◽  
Maria L Canal-Macias ◽  
Jesus M Lavado-Garcia ◽  
Raul Roncero-Martin ◽  
...  

2017 ◽  
Vol 17 (3) ◽  
pp. 424-433 ◽  
Author(s):  
Juan Cadavid-Vargas ◽  
Ignacio Leon ◽  
Susana Etcheverry ◽  
Eduardo Santi ◽  
Maria Torre ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 354
Author(s):  
Katerina Gioti ◽  
Anastasia Papachristodoulou ◽  
Dimitra Benaki ◽  
Nektarios Aligiannis ◽  
Alexios-Leandros Skaltsounis ◽  
...  

Oleuropein (OLEU) is the most distinguished phenolic compound found in olive fruit and the leaves of Olea europaea L., with several pharmacological properties, including anti-cancer actions. Adriamycin (ADR) is an anthracycline widely used as a chemotherapeutic agent, although it presents significant side effects. The aim of the present study was to investigate the effect of oleuropein alone (20 μg/mL) and in co-treatment with ADR (50 nM), in MG-63 human osteosarcoma cells. Therefore, cellular and molecular techniques, such as MTT assay, flow cytometry, real-time Polymerase Chain Reaction (PCR), western blot and Elisa method, as well as Nuclear Magnetic Resonance (NMR) spectroscopy, were applied to unveil changes in the signal transduction pathways involved in osteosarcoma cells survival. The observed alterations in gene, protein and metabolite levels denote that OLEU not only inhibits MG-63 cells proliferation and potentiates ADR’s cytotoxicity, but also exerts its action, at least in part, through the induction of autophagy.


2016 ◽  
Vol 49 (5) ◽  
pp. 1973-1982 ◽  
Author(s):  
Ran-Xi Zhang ◽  
Yang Li ◽  
Dong-Dong Tian ◽  
Yang Liu ◽  
Wu Nian ◽  
...  

2007 ◽  
Vol 68 (2) ◽  
pp. 71-78 ◽  
Author(s):  
Yih-Chau Lu ◽  
Chorng-Chih Huang ◽  
Chun-Jen Huang ◽  
Sau-Tung Chu ◽  
Chao-Chuan Chi ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document