Employing comparative QSAR techniques for the recognition of dibenzofuran and dibenzothiophene derivatives toward MMP-12 inhibition
Among various matrix metalloproteinases (MMPs), MMP-12 is one of the potential targets for cancer and other diseases. However, none of the MMP-12 inhibitors has passed the clinical trials to date. Therefore, designing potential MMP-12 inhibitors as new drug molecules can provide effective therapeutic strategies for several diseases. In this study, a series of dibenzofuran and dibenzothiophene derivatives were subjected to different 2D and 3D-QSAR techniques to point out the crucial structural contributions highly influential toward the MMP-12 inhibitory activity. These techniques identified some structural attributes of these compounds that are responsible for influencing their MMP-12 inhibition. The carboxylic group may enhance proper binding with catalytic Zn2+ ion at the MMP-12 active site. Again, the i-propyl sulfonamido carboxylic acid function contributed positively toward MMP-12 inhibition. Moreover, the dibenzofuran moiety conferred stable binding at the S1' pocket for higher MMP-12 inhibition. The steric and hydrophobic groups were found favourable near the furan ring substituted at the dibenzofuran moiety. Besides these ligand-based approaches, molecular docking and molecular dynamic (MD) simulation studies not only elucidated the importance of several aspects of these MMP-12 inhibitors while disclosing the significance of the finding of these QSAR studies and their influences toward MMP-12 inhibition. The MD simulation study also revealed stable and compact binding between such compounds at the MMP-12 active site. Therefore, the findings of these validated ligand-based and structure-based molecular modeling studies can aid the development of selective and potent lead molecules that can be used for the treatment of MMP-12-associated diseases.Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
|---|---|
| Enthalten in: |
Journal of biomolecular structure & dynamics - (2023) vom: 27. Juli, Seite 1-17 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tamang, Jigme Sangay Dorjay [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Dibenzofuran |
|---|
| Anmerkungen: |
Date Revised 27.07.2023 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1080/07391102.2023.2239923 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359981488 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359981488 | ||
| 003 | DE-627 | ||
| 005 | 20231226082030.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/07391102.2023.2239923 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1199.xml |
| 035 | |a (DE-627)NLM359981488 | ||
| 035 | |a (NLM)37498149 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tamang, Jigme Sangay Dorjay |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Employing comparative QSAR techniques for the recognition of dibenzofuran and dibenzothiophene derivatives toward MMP-12 inhibition |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 27.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Among various matrix metalloproteinases (MMPs), MMP-12 is one of the potential targets for cancer and other diseases. However, none of the MMP-12 inhibitors has passed the clinical trials to date. Therefore, designing potential MMP-12 inhibitors as new drug molecules can provide effective therapeutic strategies for several diseases. In this study, a series of dibenzofuran and dibenzothiophene derivatives were subjected to different 2D and 3D-QSAR techniques to point out the crucial structural contributions highly influential toward the MMP-12 inhibitory activity. These techniques identified some structural attributes of these compounds that are responsible for influencing their MMP-12 inhibition. The carboxylic group may enhance proper binding with catalytic Zn2+ ion at the MMP-12 active site. Again, the i-propyl sulfonamido carboxylic acid function contributed positively toward MMP-12 inhibition. Moreover, the dibenzofuran moiety conferred stable binding at the S1' pocket for higher MMP-12 inhibition. The steric and hydrophobic groups were found favourable near the furan ring substituted at the dibenzofuran moiety. Besides these ligand-based approaches, molecular docking and molecular dynamic (MD) simulation studies not only elucidated the importance of several aspects of these MMP-12 inhibitors while disclosing the significance of the finding of these QSAR studies and their influences toward MMP-12 inhibition. The MD simulation study also revealed stable and compact binding between such compounds at the MMP-12 active site. Therefore, the findings of these validated ligand-based and structure-based molecular modeling studies can aid the development of selective and potent lead molecules that can be used for the treatment of MMP-12-associated diseases.Communicated by Ramaswamy H. Sarma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a MMP-12 | |
| 650 | 4 | |a QSAR | |
| 650 | 4 | |a dibenzofuran | |
| 650 | 4 | |a dibenzothiophene | |
| 650 | 4 | |a molecular dynamic simulation | |
| 650 | 4 | |a topomer CoMFA | |
| 700 | 1 | |a Banerjee, Suvankar |e verfasserin |4 aut | |
| 700 | 1 | |a Baidya, Sandip Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh, Balaram |e verfasserin |4 aut | |
| 700 | 1 | |a Adhikari, Nilanjan |e verfasserin |4 aut | |
| 700 | 1 | |a Jha, Tarun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of biomolecular structure & dynamics |d 1985 |g (2023) vom: 27. Juli, Seite 1-17 |w (DE-627)NLM012639974 |x 1538-0254 |7 nnns |
| 773 | 1 | 8 | |g year:2023 |g day:27 |g month:07 |g pages:1-17 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/07391102.2023.2239923 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 27 |c 07 |h 1-17 | ||