Polymerizable Matrix Metalloproteinases’ Inhibitors with Potential Application for Dental Restorations

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.

Newly discovered clouting interplay between matrix metalloproteinases structures and novel quaternary Ammonium K21: computational and in-vivo testing

“…6 C). Pockets of S1’ region of various MMPs are more pronounced, less solvent exposed and are of variable sizes making them as target regions for attachment by MMP inhibitors [ 29 ]. The differences in the sizes of these pockets are attributed to the varying amino acid residues with smaller amino acids responsible for developing a large pocket and vice versa.…”

“…MMP inhibitors and QAS can be integrated into drug delivery systems for targeted delivery to oral tissues [ 8 ]. Knowing the molecular dynamics of these interactions can assist in designing effective drug delivery systems for the management of various dental diseases [ 29 , 40 ]. The growing demand for innovative antimicrobials to treat life-threatening diseases caused by the global expansion of multidrug-resistant bacterial pathogens contrasts sharply with present investment in their development, notably in the field of synthetic small molecules.…”

Potential SARS-CoV-2 3CLpro inhibitors from chromene, flavonoid and hydroxamic acid compound based on FRET assay, docking and pharmacophore studies

“…Apigenin has been reported its safety at high doses in rodent’s studies [64] , whereas, quercetin as aglycone is marketed as an ingredient of dietary supplements, therefore, it is not cytotoxic [65] . NNGH had been tested its cytotoxicity against NIH/3T3 embryonic cell and showing non-toxic potency [66] , while GC376 showed > 150 µM in its CC 50 against various cell lines reflecting its non-toxic property [67] .…”

Anti-inflammatory Activity of Polyphenols from Labisia pumila Leaves Extract

“…The same trend where gallic acid exhibited stronger binding affinity to the active site of the collagenase than ascorbic acid was also observed from the mean binding energy for both compounds as gallic acid (-5.19 kcal/mol) was lower than ascorbic acid (-3.74 kcal/mol). Both compounds docked in similar location of RO314724 in the active site of the collagenase as they formed hydrogen bonds with amino acid residues of Gly79, Leu81, Ala82, His118, Glu119, Tyr137 and Tyr140 [45][46][47] as shown in Figure 7. This docking result aligned to the experimental result in which the collagen concentration was higher when treated with gallic acid compared to ascorbic acid.…”