ADME ANALYSIS AND MOLECULAR DOCKING OF PHYTOCOMPOUNDS OF SALVIA PLEBEIA AGAINST SIRT1 TARGETS IN LUNG CANCER

CHINMAYI KRISHNA MOORTHY

doi:10.22159/ijms.2022.v10i6.46622

Authors

CHINMAYI KRISHNA MOORTHY Department of Biotechnology, NMAM Institute of Technology, Nitte, Karkala, Karnataka, India.

DOI:

https://doi.org/10.22159/ijms.2022.v10i6.46622

Keywords:

Salvia plebeia, Sirtuin, Phytochemical, Drug, Pharmacological studies

Abstract

Objective: The sirtuin family is known to have a significant role in the regulation of a wide range of physiological and pathological processes, including in neurodegeneration, age-related diseases, obesity, heart disease, and cancer, according to its targets in certain signaling pathways or in particular tumors. In the present study, the counteractive activity of 10 phytocompounds of the plant Salvia plebeia against lung cancer’s disease-causing protein SIRT1 was observed.

Methods: The molecules’ structural information was obtained using PubChem and IMPPAT websites, pharmacological assessment was done using SwissADME and toxicity was predicted using ProTox-II. A computational approach was used to study the phytochemical properties of the compounds of Salvia plebeia. Molecular docking was done using PyRx and BIOVIA helped in the visualization process.

Results: The results from the molecular docking showed that nepetin, hispidulin, and eupatorin were the most effective against SIRT1 promoting lung cancer.

Conclusion: The compounds’ ADME/T characteristics were examined to forecast their likelihood of becoming drugs. This docking study can be exploited to create powerful SIRT1 lung cancer inhibitors.

References

Rahman H, Roy B, Chowdhury GM, Hasan A, Saimun S. Medicinal plant sources and traditional healthcare practices of forest-dependent communities in and around Chunati Wildlife Sanctuary in Southeastern Bangladesh. Environ Sustain 2022;5:207-41.

Xia C, Huang Y, Qi Y, Yang X, Xue T, Hu R, et al. Developing long-term conservation priority planning for medicinal plants in China by combining conservation status with diversity hotspot analyses and climate change prediction. BMC Biol 2022;20:89.

Wang J, Xu J, Gong X, Yang M, Zhang C, Li M. Biosynthesis, chemistry, and pharmacology of polyphenols from Chinese Salvia species: A review. Molecules 2019;24:155.

Liang YY, Wan XH, Niu FJ, Xie SM, Guo H, Yang YY, et al. Salvia plebeia R. Br.: An overview about its traditional uses, chemical constituents, pharmacology and modern applications. Biomed Pharmacother 2020;121:109589.

Tran NH, Kisiel J, Roberts LR. Using cell-free DNA for HCC surveillance and prognosis. JHEP Rep 2021;3:100304.

Subbaramaiah K, Iyengar NM, Morrow M, Elemento O, Zhou XK, Dannenberg AJ. Prostaglandin E2 down-regulates sirtuin 1 (SIRT1), leading to elevated levels of aromatase, providing insights into the obesity-breast cancer connection. J Biol Chem 2019;294:361-71.

Sun S, Wang C, Weng J. MicroRNA-138-5p drives the progression of heart failure via inhibiting sirtuin 1 signaling. Mol Med Rep 2021;23:276.

Lv Y, Lin S, Peng F. SIRT1 gene polymorphisms and risk of lung cancer. Cancer Manag Res 2017;9:381-6.

Hosseninia S, Ameli A, Aslani MR, Pourfarzi F, Ghobadi H. Serum levels of sirtuin-1 in patients with lung cancer and its association with karnofsky performance status. Acta Biomed 2021;92:e2021012.

Wang C, Yang W, Dong F, Guo Y, Tan J, Ruan S, et al. The prognostic role of Sirt1 expression in solid malignancies: A meta-analysis. Oncotarget 2017;8:66343-51.

Wu S, Jiang J, Liu J, Wang X, Gan Y, Tang Y. Meta-analysis of SIRT1 expression as a prognostic marker for overall survival in gastrointestinal cancer. Oncotarget 2017;8:62589-99.

Tang BL. Sirt1’s systemic protective roles and its promise as a target in antiaging medicine. Transl Res 2011;157:276-84.

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res 2018;46:W296-303.

Pott PC, Hoffmann JP, Stiesch M, Eisenburger M. Polish of interface areas between zirconia, silicate-ceramic, and composite with diamond-containing systems. J Adv Prosthodont 2018;10:315-20.

Imholte G, Sauteraud R, Gottardo R. Analyzing peptide microarray data with the R pepStat package. Methods Mol Biol 2016;1352:127-42.

Li W, Cowley A, Uludag M, Gur T, McWilliam H, Squizzato S, et al. The EMBL-EBI bioinformatics web and programmatic tools framework. Nucleic Acids Res 2015;43:W580-4.

Laskowski RA, Jabłońska J, Pravda L, Vařeková RS, Thornton JM. PDBsum: Structural summaries of PDB entries. Protein Sci 2018;27:129-34.

Jejurikar BL, Rohane SH. Drug designing in discovery studio. Asian J Res Chem. 2021;14(2):135–8.

Deenadayalan A, Vijayalakshmi S, Janaki CS, Jayaraman S. Molecular docking analysis of stevioside with Akt and PPARγ. Bioinformation 2021;17:283-8.

Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, Chand RP, Aparna SR, Mangalapandi P, et al. IMPPAT: A curated database of Indian medicinal plants, phytochemistry and therapeutics. Sci Rep 2018;8:4329.

Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:42717.

Yang ZY, Yang ZJ, Dong J, Wang LL, Zhang LX, Ding JJ, et al. Structural analysis and identification of colloidal aggregators in drug discovery. J Chem Inf Model 2019;59:3714-26.

Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic acids Res 2018;46:W257-63.

Xu Q, Wu N, Li X, Guo C, Li C, Jiang B, et al. Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway. Cell Death Dis 2019;10:874.

Liu K, Zhao F, Yan J, Xia Z, Jiang D, Ma P. Hispidulin: A promising flavonoid with diverse anti-cancer properties. Life Sci 2020;259:118395.

Lv L, Zhang W, Li T, Jiang L, Lu X, Lin J. Hispidulin exhibits potent anticancer activity in vitro and in vivo through activating ER stress in non-small-cell lung cancer cells. Oncol Rep 2020;43:1995-2003.

Razak NA, Yeap SK, Alitheen NB, Ho WY, Yong CY, Tan SW, et al. Eupatorin suppressed tumor progression and enhanced immunity in a 4t1 murine breast cancer model. Integr Cancer Ther 2020;19:1534735420935625.

Choi JG, Kim YS, Kim JH, Kim TI, Li W, Oh TW, et al. Anticancer effect of Salvia plebeia and its active compound by improving T-cell activity via blockade of PD-1/PD-L1 interaction in humanized PD-1 mouse model. Front Immunol 2020;11:598556.

Alves-Fernandes DK, Jasiulionis MG. The role of SIRT1 on DNA damage response and epigenetic alterations in cancer. Int J Mol Sci 2019;20:3153.

Frazzi R. SIRT1 in secretory organ cancer. Front Endocrinol 2018;9:569.