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Matrix metalloproteinase-12 inhibitors: synthesis, structure-activity relationships and intestinal absorption of novel sugar-based biphenylsulfonam…

A new interesting article has been published in Bioorg Med Chem. 2018 Dec 1;26(22):5804-5815. doi: 10.1016/j.bmc.2018.10.024. Epub 2018 Oct 26. and titled:

Matrix metalloproteinase-12 inhibitors: synthesis, structure-activity relationships and intestinal absorption of novel sugar-based biphenylsulfonam…

Authors of this article are:

Cuffaro D, Camodeca C, D’Andrea F, Piragine E, Testai L, Calderone V, Orlandini E, Nuti E, Rossello A.

A summary of the article is shown below:

MMP-12 is a validated target in pulmonary and cardiovascular diseases. The principal obstacles to clinical development of MMP-12 inhibitors are an inadequate selectivity for the target enzyme and a poor water solubility, with consequent poor oral bioavailability. We recently reported a new class of sugar-based arylsulfonamide carboxylates with a nanomolar activity for MMP-12, a good selectivity and an improved water solubility. In this study, we designed and synthesized new derivatives to characterize the structure-activity relationship (SAR) within this class of glycoconjugate inhibitors. All the new derivatives were tested on human recombinant MMP-12 and MMP-9 in order to evaluate their affinity and the selectivity for the target enzyme. Among them, the four most promising compounds were selected to assess their intestinal permeability using an ex vivo everted gut sac model. Given the high polarity and structural similarity to glucose, compound 3 was demonstrated to cross the intestinal membrane by using the facilitative GLUT2 transport.

Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as:

Glucose transporters;Glycoconjugates;Intestinal permeability;MMP-12 inhibitors

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