Abstract
Collagen cleavage by matrix metalloproteinase (MMP) is considered a major cause of dental resins long term failure. Most MMP inhibitors display significant toxicity and are unsuitable for dental resins’ applications. Here we report a study of a new class of inhibitors that display the unique property of being co-polymerizable with other vinyl compounds present in commercial dental resins, limiting their release and potential toxicity. Computational affinity towards the active site of different MMP-1; -2; -8; -9 and -13 of several compounds showed interesting properties and were synthesized. These free compounds were tested concerning their toxicity upon contact with two different cell types, with no substantial decrease in cell viability at high concentrations. Even so, compound’s safety can be further improved upon copolymerization with commercial dental resins, limiting their release.
Highlights
For drug development, the number of the hydrogen bonds donors may be more crucial than the number of hydrogen bonds acceptors since compounds with more hydrogen bonds acceptors have more favorable profiles related to bioavailability and membrane permeability [45,48,51,52]
Compounds A, B and C present some toxicity towards the two cell types, it may be much less as compounds are to be used copolymerization with dental resins, which reduce their free concentration
Preliminary results by FTIR spectroscopy using commercial resins showed a decrease in the vinyl bands of the free compounds upon light polymerization
Summary
The matrix metalloproteinases (MMPs) belong to the Metzincs superfamily [1,2,3,4,5,6,7,8], and are characterized by a common conserved catalytic domain: VAAHExGHxxGxxH [2,5,6,7,9,10,11,12,13,14]. The principal biologic function of MMPs is degradation of extracellular matrix (ECM) proteins and glycoproteins, membrane receptors, cytokines and growth factors [1,2,3,5,6,7,8,11,13,14,16,20,21,22,23,24] They are involved in several biologic processes [1,2,7,8,10,11,13,15,16,23,25,26] and their deregulation leads to the progression of various pathologies [1,2,8,13,14,19,23]. In mouse embryo NIH/3T3 fibroblast cells and human MG-63 osteoblast-like cells
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