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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Sep 28

PMID 34576138

Citations 3

Authors

Jose Maria Zapico

Lourdes Acosta

Miryam Pastor

Loganathan Rangasamy

Laura Marquez-Cantudo

Claire Coderch

Irene Ortin

Maria Nicolau-Sanus

Leonor Puchades-Carrasco

Antonio Pineda-Lucena

Alejandro Majali-Martinez

Pilar Ramos

Beatriz de Pascual-Teresa

Ana Ramos

Affiliations

Soon will be listed here.

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 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 has been identified as a water-soluble and highly potent inhibitor with activity in MG-63 human osteosarcoma cells.

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