NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2021, Vol. 33 ›› Issue (4): 543-553.doi: 10.16333/j.1001-6880.2021.4.002

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Analysis of the potentiality of dehydroabietic acid as PI3K/AKT/mTOR signaling pathway inhibitor based on computational simulation

LI Cui-ping1,CHEN Nai-yuan2,4*,LI Xin-yu3,LU Guo-dong2,4   

  1. 1School of Stomatology,Guangxi Medical University;2School of Public Health,Guangxi Medical University;3School of Preclinical Medicine,Guangxi Medical University;4Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases,Guangxi Medical University,Nanning 530021,China

  • Online:2021-04-28 Published:2021-05-10

Abstract:

To study the inhibitory ability of dehydroabietic acid (DHA) against PI3K/AKT/mTOR signaling pathway,molecular docking was used to predict the binding abilities and the binding modes of DHA with the pathway proteins,western blot was performed to confirm the expressions of the pathway proteins affected by DHA,the “pkCSM-pharmacokinetics” online web-server was chosen for predictions of drug-likeness and pharmacokinetic properties of DHA.The molecular docking results showed that DHA could bind with the pathway proteins because the lowest binding energies of the predicted conformations are not higher than -6.16 kcal/mol.The western blot showed that in the presence of DHA,the expression of p85,the regulatory subunit of PI3K,was decreased obviously;the phosphorylations of AKT and mTOR were inhibited significantly;the expressions of phosphorylated downstream effectors were also inhibited in varying degrees.In the drug-likeness and pharmacokinetic predictions,DHA passes most of the tests.On the whole,DHA may be used as a therapeutic candidate against PI3K/AKT/mTOR signaling pathway.

Key words: dehydroabietic acid, PI3K/AKT/mTOR, inhibitor, computational simulation

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