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Searching for Natural Aurora a Kinase Inhibitors from Peppers Using Molecular Docking and Molecular Dynamics.

ABSTRACT: Natural products are the precursors of many medicinal substances. Peppers (Piper, Capsicum, Pimienta) are a rich source of compounds with potential multidirectional biological activity. One of the studied directions is antitumor activity. Little research has been carried out so far on the ability of the compounds contained in peppers to inhibit the activity of Aurora A kinase, the overexpression of which is characteristic of cancer development. In this study, molecular docking methods, as well as molecular dynamics, were used, looking for compounds that could inhibit the activity of Aurora A kinase and trying to determine whether there is a relationship between the stimulation of the TRPV1 receptor and the inhibition of Aurora A kinase. We compared our results with anticancer activity studied earlier on MCF-7 cell lines (breast cancer cells). Our research indicates that the compounds contained in peppers can inhibit Aurora A. Further in vitro research is planned to confirm the obtained results.

SUBMITTER: Siudem P

PROVIDER: S-EPMC10674409 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Searching for Natural Aurora a Kinase Inhibitors from Peppers Using Molecular Docking and Molecular Dynamics.

Siudem Paweł P Szeleszczuk Łukasz Ł Paradowska Katarzyna K

Pharmaceuticals (Basel, Switzerland) 20231031 11

Natural products are the precursors of many medicinal substances. Peppers (<i>Piper</i>, <i>Capsicum, Pimienta</i>) are a rich source of compounds with potential multidirectional biological activity. One of the studied directions is antitumor activity. Little research has been carried out so far on the ability of the compounds contained in peppers to inhibit the activity of Aurora A kinase, the overexpression of which is characteristic of cancer development. In this study, molecular docking meth ...[more]

PMID: 38004405

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Project description:The aurora kinase is a key enzyme that is implicated in tumor growth. Research revealed that small molecules that target aurora kinase have beneficial effects as anticancer agents. In the present study, in order to identify potential antibreast cancer agents with aurora kinase inhibitory activity, we employed QSARINS software to perform the quantitative structure-activity relationship (QSAR). The statistical values resulted from the study include R2 = 0.8902, CCCtr = 0.7580, Q2 LOO = 0.7875, Q2LMO = 0.7624, CCCcv = 0.7535, R2ext = 0.8735, and CCCext = 0.8783. Among the four generated models, the two best models encompass five important variables, including PSA, EstateVSA5, MoRSEP3, MATSp5, and RDFC24. The parameters including the atomic volume, atomic charges, and Sanderson's electronegativity played an important role in designing newer lead compounds. Based on the above data, we have designed six series of compounds including 1a-e, 2a-e, 3a-e, 4a-e, 5a-e, and 6a-e. All these compounds were subjected to molecular docking studies by using AutoDock v4.2.6 against the aurora kinase protein (1MQ4). Among the above 30 compounds, the 2-amino thiazole derivatives 1a, 2a, 3e, 4d, 5d, and 6d have excellent binding interactions with the active site of 1MQ4. Compound 1a had the highest docking score (-9.67) and hence was additionally subjected to molecular dynamic simulation investigations for 100 ns. The stable binding of compound 1a with 1MQ4 was verified by RMSD, RMSF, RoG, H-bond, molecular mechanics-generalized Born surface area (MM-GBSA), free binding energy calculations, and solvent-accessible surface area (SASA) analyses. Furthermore, newly designed compound 1a exhibited excellent ADMET properties. Based on the above findings, we propose that the designed compound 1a may be utilized as the best theoretical lead for future experimental research of selective inhibition of aurora kinase, therefore assisting in the creation of new antibreast cancer drugs.

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Searching for Natural Aurora a Kinase Inhibitors from Peppers Using Molecular Docking and Molecular Dynamics.

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Searching for Natural Aurora a Kinase Inhibitors from Peppers Using Molecular Docking and Molecular Dynamics.

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