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Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches

Bladder cancer (BC) is the 10th most common tumour with a high incidence and recurrence rate worldwide; however, the current therapies present limitations as, regularly, not all patients benefit from treatment. Therefore, the search for new, active marine phenolic acids with anti-tumour properties i...

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Main Authors: Roney, Miah, Uddin, Md. Nazim, Mohd Fadhlizil Fasihi, Mohd Aluwi
Format: Article
Language:English
English
Published: Elsevier Ltd 2024
Subjects:
HD Industries. Land use. Labor
Online Access:http://umpir.ump.edu.my/id/eprint/42376/1/Comprehending%20the%20pharmacological%20mechanism%20of%20marine%20phenolic%20acids%20in%20bladder%20cancer%20therapy%20against%20matrix%20metalloproteinase%209%20protein%20by%20integrated%20network%20pharmacology.pdf
http://umpir.ump.edu.my/id/eprint/42376/2/Comprehending%20the%20pharmacological%20mechanism%20of%20marine%20phenolic%20acids%20in%20bladder%20cancer%20therapy%20against%20matrix%20metalloproteinase%209%20protein%20by%20integrated%20network%20pharmacology%20and%20in-silico%20approaches.pdf
http://umpir.ump.edu.my/id/eprint/42376/
https://doi.org/10.1016/j.compbiolchem.2024.108149
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spelling my.ump.umpir.423762024-08-16T01:46:09Z http://umpir.ump.edu.my/id/eprint/42376/ Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches Roney, Miah Uddin, Md. Nazim Mohd Fadhlizil Fasihi, Mohd Aluwi HD Industries. Land use. Labor Bladder cancer (BC) is the 10th most common tumour with a high incidence and recurrence rate worldwide; however, the current therapies present limitations as, regularly, not all patients benefit from treatment. Therefore, the search for new, active marine phenolic acids with anti-tumour properties is imperative. In this study, we subjected marine phenolic acids to in silico investigations such as network pharmacology, molecular docking, and molecular dynamics simulation (MD) to identify a plausible pathway and the lead compound that inhibits BC. According to the network pharmacology analysis, eight hub genes (PLAU, MMP2, ITGB3, MAPK1, PTPN11, ESR1, TLR4, MMP9) were found and linked to the enrichment of hsa05205: proteoglycans in cancer, and four hub genes (MMP1, MMP2, MAPK1, MMP9) were involved in the enrichment of hsa05219: BC. Subsequently, molecular docking studies showed that the marine phenolic acids exhibit a strong binding affinity for the target protein, matrix metalloproteinase-9 (MPP9). Among these 14 marine phenolic acids, chicoric acid showed the highest binding affinity of −67.1445 kcal/mol and formed hydrogen bonds with the residues of Ala189, Gln227, Leu188, His226, Ala242, Arg249, Ala191, and Gly186 in the active site of the MPP9 protein. Then, molecular dynamics simulation revealed that chicoric acid formed a stable protein-ligand complex with RMSD and RMSF values of 0.72 nm and 0.53 nm, respectively. Furthermore, the PCA method was employed to understand the dynamical behaviour in the conformational space of MPP9 protein bound to chicoric acid, and the results showed the good conformational space behaviour of MPP9 protein. Moreover, chicoric acid showed a free binding energy value of −32.62 kcal/mol, which indicated it could be a BC inhibitor. Overall, chicoric acid demonstrated potential anti-BC activity through MPP9 protein inhibition. Elsevier Ltd 2024 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/42376/1/Comprehending%20the%20pharmacological%20mechanism%20of%20marine%20phenolic%20acids%20in%20bladder%20cancer%20therapy%20against%20matrix%20metalloproteinase%209%20protein%20by%20integrated%20network%20pharmacology.pdf pdf en http://umpir.ump.edu.my/id/eprint/42376/2/Comprehending%20the%20pharmacological%20mechanism%20of%20marine%20phenolic%20acids%20in%20bladder%20cancer%20therapy%20against%20matrix%20metalloproteinase%209%20protein%20by%20integrated%20network%20pharmacology%20and%20in-silico%20approaches.pdf Roney, Miah and Uddin, Md. Nazim and Mohd Fadhlizil Fasihi, Mohd Aluwi (2024) Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches. Computational Biology and Chemistry, 112 (108149). pp. 1-12. ISSN 1476-9271. (Published) https://doi.org/10.1016/j.compbiolchem.2024.108149 10.1016/j.compbiolchem.2024.108149
institution Universiti Malaysia Pahang Al-Sultan Abdullah
building UMPSA Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Pahang Al-Sultan Abdullah
content_source UMPSA Institutional Repository
url_provider http://umpir.ump.edu.my/
language English
English
topic HD Industries. Land use. Labor
spellingShingle HD Industries. Land use. Labor
Roney, Miah
Uddin, Md. Nazim
Mohd Fadhlizil Fasihi, Mohd Aluwi
Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches
description Bladder cancer (BC) is the 10th most common tumour with a high incidence and recurrence rate worldwide; however, the current therapies present limitations as, regularly, not all patients benefit from treatment. Therefore, the search for new, active marine phenolic acids with anti-tumour properties is imperative. In this study, we subjected marine phenolic acids to in silico investigations such as network pharmacology, molecular docking, and molecular dynamics simulation (MD) to identify a plausible pathway and the lead compound that inhibits BC. According to the network pharmacology analysis, eight hub genes (PLAU, MMP2, ITGB3, MAPK1, PTPN11, ESR1, TLR4, MMP9) were found and linked to the enrichment of hsa05205: proteoglycans in cancer, and four hub genes (MMP1, MMP2, MAPK1, MMP9) were involved in the enrichment of hsa05219: BC. Subsequently, molecular docking studies showed that the marine phenolic acids exhibit a strong binding affinity for the target protein, matrix metalloproteinase-9 (MPP9). Among these 14 marine phenolic acids, chicoric acid showed the highest binding affinity of −67.1445 kcal/mol and formed hydrogen bonds with the residues of Ala189, Gln227, Leu188, His226, Ala242, Arg249, Ala191, and Gly186 in the active site of the MPP9 protein. Then, molecular dynamics simulation revealed that chicoric acid formed a stable protein-ligand complex with RMSD and RMSF values of 0.72 nm and 0.53 nm, respectively. Furthermore, the PCA method was employed to understand the dynamical behaviour in the conformational space of MPP9 protein bound to chicoric acid, and the results showed the good conformational space behaviour of MPP9 protein. Moreover, chicoric acid showed a free binding energy value of −32.62 kcal/mol, which indicated it could be a BC inhibitor. Overall, chicoric acid demonstrated potential anti-BC activity through MPP9 protein inhibition.
format Article
author Roney, Miah
Uddin, Md. Nazim
Mohd Fadhlizil Fasihi, Mohd Aluwi
author_facet Roney, Miah
Uddin, Md. Nazim
Mohd Fadhlizil Fasihi, Mohd Aluwi
author_sort Roney, Miah
title Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches
title_short Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches
title_full Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches
title_fullStr Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches
title_full_unstemmed Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches
title_sort comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches
publisher Elsevier Ltd
publishDate 2024
url http://umpir.ump.edu.my/id/eprint/42376/1/Comprehending%20the%20pharmacological%20mechanism%20of%20marine%20phenolic%20acids%20in%20bladder%20cancer%20therapy%20against%20matrix%20metalloproteinase%209%20protein%20by%20integrated%20network%20pharmacology.pdf
http://umpir.ump.edu.my/id/eprint/42376/2/Comprehending%20the%20pharmacological%20mechanism%20of%20marine%20phenolic%20acids%20in%20bladder%20cancer%20therapy%20against%20matrix%20metalloproteinase%209%20protein%20by%20integrated%20network%20pharmacology%20and%20in-silico%20approaches.pdf
http://umpir.ump.edu.my/id/eprint/42376/
https://doi.org/10.1016/j.compbiolchem.2024.108149
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score 13.235362

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