Investigation of inhibitory properties of triphenyl-LasR enzyme involved in the quorum sensing of Pseudomonas aeruginosa by molecular modeling
الموضوعات :
Mahshad Shahriari
1
(Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Evin, Tehran, Iran)
Faezeh Nourmandipour
2
(Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Evin, Tehran, Iran)
Samira Norouzi
3
(Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Evin, Tehran, Iran)
Samad Nejad Ebrahimi
4
(Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Evin, Tehran, Iran)
الکلمات المفتاحية: Molecular docking, pharmacophore, MM-GBSA, QSAR, Quorum sensing, Biofilm formation,
ملخص المقالة :
Quorum sensing (QS) is a bacterial communication mechanism that regulates the production of many pathogenic factors, including the formation of pigments and the ability to form biofilms that are essential for chronic infections. For discovering new inhibitors on the formation of biofilm formation, over 700 synthetic and natural compounds have been virtually screened against the triphenyl-LasR enzyme involved in Pseudomonas aeruginosa’s QS system. The 3D-QSAR studies revealed the relationship between the quantitative structure of compounds and their activity. The drug-like properties of compounds and effective pharmacophore features on the ligand interaction with protein were investigated by ADME and E-pharmacophore analysis. According to the obtained results, we identified compound with PubChem ID 118732838 with the glide score of -12.34 kcal/mol and oral absorption of 58.75% as the potential compound for inhibiting triphenyl-LasR protein. The study outcomes can help us to identify new drugs to inhibit biofilm formation and decrease bacterial resistance.
Akkerman-Nijland, A.M., Yousofi, M., Rottier, B.L., Van der Vaart, H., Burgerhof, J.G., Frijlink, H.W., Touw, D.J., Koppelman, G.H., Akkerman, O.W., 2020. Eradication of Pseudomonas aeruginosa in cystic fibrosis patients with inhalation of dry powder tobramycin. Ther. Adv. Respir. Dis. 14, 1753466620905279.
Al-Bagawi, A.H., Bayoumy, A.M., Ibrahim, M.A., 2020. Molecular modeling analyses for graphene functionalized with Fe3O4 and NiO. Heliyon 6(7), e04456.
Aliyu, A.B., Koorbanally, N.A., Moodley, B., Singh, P., Chenia, H.Y., 2016. Quorum sensing inhibitory potential and molecular docking studies of sesquiterpene lactones from Vernonia blumeoides. Phytochemistry 126, 23-33.
Chintha, C., Carlesso, A., Gorman, A.M., Samali, A., Eriksson, L.A., 2020. Molecular modeling provides a structural basis for PERK inhibitor selectivity towards RIPK1. RSC Adv. 10(1), 367-375.
de Kievit, T.R., Kakai, Y., Register, J.K., Pesci, E.C., Iglewski, B.H., 2002. Role of the Pseudomonas aeruginosa las and rhl quorum-sensing systems in rhlI regulation. FEMS Microbiol. Lett. 212(1), 101-106.
Fuqua, C., Greenberg, E.P., 2002. Listening in on bacteria: acyl-homoserine lactone signalling. Nat. Rev. Mol. Cell Biol. 3(9), 685-695.
Ganjoo, A., Prabhakar, C., 2019. In silico structural anatomization of spleen tyrosine kinase inhibitors: Pharmacophore modeling, 3D QSAR analysis and molecular docking studies. J. Mol. Struct. 1189, 102-111.
Gerdt, J.P., McInnis, C.E., Schell, T.L., Rossi, F.M., Blackwell, H.E., 2014. Mutational analysis of the quorum-sensing receptor LasR reveals interactions that govern activation and inhibition by nonlactone ligands. Chem. Biol. 21(10), 1361-1369.
Ho, D.K., Murgia, X., De Rossi, C., Christmann, R., Hüfner de Mello Martins, A.G., Koch, M., Andreas, A., Herrmann, J., Müller, R., Empting, M., 2020. Squalenyl hydrogen sulfate nanoparticles for simultaneous delivery of tobramycin and an alkylquinolone quorum sensing inhibitor enable the eradication of P. aeruginosa biofilm infections. Angew. Chem. - Int. Ed. 59(26), 10292-10296.
Kiratisin, P., Tucker, K.D., Passador, L., 2002. LasR, a transcriptional activator of Pseudomonas aeruginosa virulence genes, functions as a multimer. J. Bacteriol. 184(17), 4912-4919.
Li, Z., Nair, S.K., 2012. Quorum sensing: how bacteria can coordinate activity and synchronize their response to external signals? Protein Sci. 21(10), 1403-1417.
Manson, D.E., O’Reilly, M.C., Nyffeler, K.E., Blackwell, H.E., 2020. Design, synthesis, and biochemical characterization of non-native antagonists of the Pseudomonas aeruginosa quorum sensing receptor LasR with nanomolar IC50 values. ACS Infect. Dis. 6(4), 649-661.
Mizdal, C.R., Stefanello, S.T., Nogara, P.A., Soares, F.A.A., de Lourenço Marques, L., de Campos, M.M.A., 2018. Molecular docking, and anti-biofilm activity of gold-complexed sulfonamides on Pseudomonas aeruginosa. Microb. Pathog. 125, 393-400.
Norouzi, S., Farahani, M., Nejad Ebrahimi, S., 2021. The integration of pharmacophore-based 3D QSAR modeling and virtual screening in identification of natural product inhibitors against SARS-CoV-2. Pharm. Sci.
O’Brien, K.T., Noto, J.G., Nichols-O’Neill, L., Perez, L.J., 2015. Potent irreversible inhibitors of LasR quorum sensing in Pseudomonas aeruginosa. ACS Med. Chem. Lett. 6(2), 162-167.
Pejin, B., Ciric, A., Dimitric Markovic, J., Glamoclija, J., Nikolic, M., Sokovic, M., 2017. An insight into anti-biofilm and anti-quorum sensing activities of the selected anthocyanidins: The case study of Pseudomonas aeruginosa PAO1. Nat. Prod. Res. 31(10), 1177-1180.
Pejin, B., Ciric, A., Glamoclija, J., Nikolic, M., Sokovic, M., 2015a. In vitro anti-quorum sensing activity of phytol. Nat. Prod. Res. 29(4), 374-377.
Pejin, B., Ciric, A., Glamoclija, J., Nikolic, M., Stanimirovic, B., Sokovic, M., 2015b. Quercetin potently reduces biofilm formation of the strain Pseudomonas aeruginosa PAO1 in vitro. Curr. Pharm. Biotechnol. 16(8), 733-737.
Pejin, B., Iodice, C., Tommonaro, G., Stanimirovic, B., Ciric, A., Glamoclija, J., Nikolic, M., De Rosa, S., Sokovic, M., 2014. Further in vitro evaluation of antimicrobial activity of the marine sesquiterpene hydroquinone avarol. Curr. Pharm. Biotechnol. 15(6), 583-588.
Subhani, S., Jamil, K., 2015. Molecular docking of chemotherapeutic agents to CYP3A4 in non-small cell lung cancer. Biomed. Pharmacother. 73, 65-74.
Vora, J., Patel, S., Sinha, S., Sharma, S., Srivastava, A., Chhabria, M., Shrivastava, N., 2019. Molecular docking, QSAR and ADMET based mining of natural compounds against prime targets of HIV. J. Biomol. Struct. Dyn. 37(1), 131-146.
Zou, Y., Nair, S.K., 2009. Molecular basis for the recognition of structurally distinct autoinducer mimics by the Pseudomonas aeruginosa LasR quorum-sensing signaling receptor. Cell Chem. Biol. 16(9), 961-970.
