dc.contributor.author | Rahman, Fatema | |
dc.contributor.author | Wushur, Imin | |
dc.contributor.author | Malla, Nabin | |
dc.contributor.author | Åstrand, Ove Alexander Høgmoen | |
dc.contributor.author | Rongved, Pål | |
dc.contributor.author | Winberg, Jan-Olof | |
dc.contributor.author | Sylte, Ingebrigt | |
dc.date.accessioned | 2022-01-21T11:50:57Z | |
dc.date.available | 2022-01-21T11:50:57Z | |
dc.date.issued | 2021-12-22 | |
dc.description.abstract | Inhibition of bacterial virulence is believed to be a new treatment option for bacterial
infections. In the present study, we tested dipicolylamine (DPA), tripicolylamine (TPA), tris pyridine
ethylene diamine (TPED), pyridine and thiophene derivatives as putative inhibitors of the bacterial
virulence factors thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) and the human zinc
metalloproteases, matrix metalloprotease-9 (MMP-9) and matrix metalloprotease-14 (MMP-14). These
compounds have nitrogen or sulfur as putative donor atoms for zinc chelation. In general, the
compounds showed stronger inhibition of MMP-14 and PLN than of the other enzymes, with Ki
values in the lower µM range. Except for DPA, none of the compounds showed significantly stronger
inhibition of the virulence factors than of the human zinc metalloproteases. TPA and Zn230 were
the only compounds that inhibited all five zinc metalloproteinases with a Ki value in the lower µM
range. The thiophene compounds gave weak or no inhibition. Docking indicated that some of the
compounds coordinated zinc by one oxygen atom from a hydroxyl or carbonyl group, or by oxygen
atoms both from a hydroxyl group and a carbonyl group, and not by pyridine nitrogen as in DPA
and TPA. | en_US |
dc.identifier.citation | Rahman, Wushur, Malla, Åstrand, Rongved, Winberg, Sylte. Zinc-Chelating Compounds as Inhibitors of Human and Bacterial Zinc Metalloproteases. Molecules. 2021 | en_US |
dc.identifier.cristinID | FRIDAID 1985941 | |
dc.identifier.doi | 10.3390/molecules27010056 | |
dc.identifier.issn | 1420-3049 | |
dc.identifier.uri | https://hdl.handle.net/10037/23748 | |
dc.language.iso | eng | en_US |
dc.publisher | MDPI | en_US |
dc.relation.ispartof | Rahman, F.A. (2023). Zinc binding and chelating compounds as inhibitors of bacterial metalloproteases and human matrix metalloproteases. (Doctoral thesis). <a href=https://hdl.handle.net/10037/31269>https://hdl.handle.net/10037/31269</a>. | |
dc.relation.journal | Molecules | |
dc.relation.projectID | Helseforetak: HNF1514-20 | en_US |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2021 The Author(s) | en_US |
dc.title | Zinc-Chelating Compounds as Inhibitors of Human and Bacterial Zinc Metalloproteases | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |