Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds
Compounds containg catechol or bisphosphonate were tested as inhibitors of the zinc metalloproteases, thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) which are bacterial virulence factors, and the human matrix metalloproteases MMP-9 and −14. Inhibition of virulence is a putative strategy i...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1901088 |
| _version_ | 1828127075164225536 |
|---|---|
| author | Fatema Rahman Tra-Mi Nguyen Olayiwola A. Adekoya Cristina Campestre Paolo Tortorella Ingebrigt Sylte Jan-Olof Winberg |
| author_facet | Fatema Rahman Tra-Mi Nguyen Olayiwola A. Adekoya Cristina Campestre Paolo Tortorella Ingebrigt Sylte Jan-Olof Winberg |
| author_sort | Fatema Rahman |
| collection | DOAJ |
| description | Compounds containg catechol or bisphosphonate were tested as inhibitors of the zinc metalloproteases, thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) which are bacterial virulence factors, and the human matrix metalloproteases MMP-9 and −14. Inhibition of virulence is a putative strategy in the development of antibacterial drugs, but the inhibitors should not interfere with human enzymes. Docking indicated that the inhibitors bound MMP-9 and MMP-14 with the phenyl, biphenyl, chlorophenyl, nitrophenyl or methoxyphenyl ringsystem in the S1′-subpocket, while these ringsystems entered the S2′- or S1 -subpockets or a region involving amino acids in the S1′- and S2′-subpockets of the bacterial enzymes. An arginine conserved among the bacterial enzymes seemed to hinder entrance deeply into the S1′-subpocket. Only the bisphosphonate containing compound RC2 bound stronger to PLN and TLN than to MMP-9 and MMP-14. Docking indicated that the reason was that the conserved arginine (R203 in TLN and R198 in PLN) interacts with phosphate groups of RC2. |
| first_indexed | 2024-04-11T15:44:50Z |
| format | Article |
| id | doaj.art-7eeccc7a14684fc499144409657fb717 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-11T15:44:50Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7eeccc7a14684fc499144409657fb7172022-12-22T04:15:37ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136181983010.1080/14756366.2021.19010881901088Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compoundsFatema Rahman0Tra-Mi Nguyen1Olayiwola A. Adekoya2Cristina Campestre3Paolo Tortorella4Ingebrigt Sylte5Jan-Olof Winberg6Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of NorwayDepartment of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of NorwayDepartment of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of NorwayDepartment of Pharmacy, University of “G. d’Annunzio” ChietiDepartment of Pharmacy, Science of Pharmacy, University “A. Moro” BariDepartment of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of NorwayDepartment of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of NorwayCompounds containg catechol or bisphosphonate were tested as inhibitors of the zinc metalloproteases, thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) which are bacterial virulence factors, and the human matrix metalloproteases MMP-9 and −14. Inhibition of virulence is a putative strategy in the development of antibacterial drugs, but the inhibitors should not interfere with human enzymes. Docking indicated that the inhibitors bound MMP-9 and MMP-14 with the phenyl, biphenyl, chlorophenyl, nitrophenyl or methoxyphenyl ringsystem in the S1′-subpocket, while these ringsystems entered the S2′- or S1 -subpockets or a region involving amino acids in the S1′- and S2′-subpockets of the bacterial enzymes. An arginine conserved among the bacterial enzymes seemed to hinder entrance deeply into the S1′-subpocket. Only the bisphosphonate containing compound RC2 bound stronger to PLN and TLN than to MMP-9 and MMP-14. Docking indicated that the reason was that the conserved arginine (R203 in TLN and R198 in PLN) interacts with phosphate groups of RC2.http://dx.doi.org/10.1080/14756366.2021.1901088zinc proteasesbacterial virulence factorsmatrix metalloproteasesenzyme inhibitiondocking and scoring |
| spellingShingle | Fatema Rahman Tra-Mi Nguyen Olayiwola A. Adekoya Cristina Campestre Paolo Tortorella Ingebrigt Sylte Jan-Olof Winberg Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds Journal of Enzyme Inhibition and Medicinal Chemistry zinc proteases bacterial virulence factors matrix metalloproteases enzyme inhibition docking and scoring |
| title | Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds |
| title_full | Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds |
| title_fullStr | Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds |
| title_full_unstemmed | Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds |
| title_short | Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds |
| title_sort | inhibition of bacterial and human zinc metalloproteases by bisphosphonate and catechol containing compounds |
| topic | zinc proteases bacterial virulence factors matrix metalloproteases enzyme inhibition docking and scoring |
| url | http://dx.doi.org/10.1080/14756366.2021.1901088 |
| work_keys_str_mv | AT fatemarahman inhibitionofbacterialandhumanzincmetalloproteasesbybisphosphonateandcatecholcontainingcompounds AT traminguyen inhibitionofbacterialandhumanzincmetalloproteasesbybisphosphonateandcatecholcontainingcompounds AT olayiwolaaadekoya inhibitionofbacterialandhumanzincmetalloproteasesbybisphosphonateandcatecholcontainingcompounds AT cristinacampestre inhibitionofbacterialandhumanzincmetalloproteasesbybisphosphonateandcatecholcontainingcompounds AT paolotortorella inhibitionofbacterialandhumanzincmetalloproteasesbybisphosphonateandcatecholcontainingcompounds AT ingebrigtsylte inhibitionofbacterialandhumanzincmetalloproteasesbybisphosphonateandcatecholcontainingcompounds AT janolofwinberg inhibitionofbacterialandhumanzincmetalloproteasesbybisphosphonateandcatecholcontainingcompounds |