Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Zapico, JM; Acosta, L; Pastor, M; Rangasamy, L; Marquez-Cantudo, L; Coderch, C; Ortin, I; Nicolau-Sanus, M; Puchades-Carrasco, L; Pineda-Lucena, A; Majali-Martinez, A; Ramos, P; de Pascual-Teresa, B; Ramos, A.
Design and Synthesis of Water-Soluble and Potent MMP-13 Inhibitors with Activity in Human Osteosarcoma Cells
INT J MOL SCI. 2021; 22(18): 9976
Doi: 10.3390/ijms22189976
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- Co-authors Med Uni Graz
- Majali Martinez Alejandro
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- Abstract:
- 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.
- Find related publications in this database (Keywords)
- MMP-13 inhibitors
- metalloproteinases
- osteoarthritis
- molecular modeling
- RMN
- organic synthesis