Structural profile of collagenase inhibitors

Introduction: Bacterial collagenases are an important virulence factors in a variety of pathogenic bacteria. The purpose of this research was to identify the best structural profile for a collagenase inhibitor. Methods: A group of 253 compounds with collagenase inhibitory activity was extracted from ChEMBL data base and curated to possess exact values of the Ki parameter (pKi), a numeric value for inhibitory potency. A series of molecular descriptors and Bemis-Murcko scaffolds were computed using Data Warrior 5.2.1 software. Results: All the compounds analysed contain at least 1 donor and at least 8 hydrogen bond acceptors and at least one aromatic ring, which is very often a benzene. The molecule’s size doesn’t seem to directly influence the potency of the inhibition. A series of pharmacophore groups were identified and discuss: o-nitrobenzene, hydroxamic acid, sulphonamide. Most inhibitors are based on two aromatic structures, either two benzene rings or a benzene nucleus and a naphthalene nucleus, joined by a bridge of at least 3 atoms. Conclusion: The highlighted structural elements are very specific, making it difficult to identify new candidates as collagenase inhibitors. The observation of bioisosterism relationships between certain structural fragments may allow the application of isosteric analogy changes to the design of new collagenase inhibitors.