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.

Autor: Roney M; Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Persiaran Tun Khalil Yaakob, Kuantan, Pahang, Malaysia; Centre for Bio-aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Persiaran Tun Khalil Yaakob, Kuantan, Pahang, Malaysia., Uddin MN; Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research, Dhaka 1205, Bangladesh., Fasihi Mohd Aluwi MF; Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Persiaran Tun Khalil Yaakob, Kuantan, Pahang, Malaysia; Centre for Bio-aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Persiaran Tun Khalil Yaakob, Kuantan, Pahang, Malaysia. Electronic address: fasihi@umpsa.edu.my.
Jazyk: angličtina
Zdroj: Computational biology and chemistry [Comput Biol Chem] 2024 Oct; Vol. 112, pp. 108149. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.compbiolchem.2024.108149
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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