Tetraprenyltoluquinone Inhibits the Tumor Marker Aldo-Keto Reductase: An in Silico Study

Dira Hefni (1), - Dachriyanus (2), Meri Susanti (3), Fatma Sri Wahyuni (4), Fajar Arya Pratama (5)
(1) Faculty of Pharmacy, Andalas University, Kampus Limau Manis, 25163, Padang, West Sumatra, Indonesia
(2) Faculty of Pharmacy, Andalas University, Kampus Limau Manis, 25163, Padang, West Sumatra, Indonesia
(3) Faculty of Pharmacy, Andalas University, Kampus Limau Manis, 25163, Padang, West Sumatra, Indonesia
(4) Faculty of Pharmacy, Andalas University, Kampus Limau Manis, 25163, Padang, West Sumatra, Indonesia
(5) Faculty of Pharmacy, Andalas University, Kampus Limau Manis, 25163, Padang, West Sumatra, Indonesia
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How to cite (IJASEIT) :
Hefni, Dira, et al. “Tetraprenyltoluquinone Inhibits the Tumor Marker Aldo-Keto Reductase: An in Silico Study”. International Journal on Advanced Science, Engineering and Information Technology, vol. 12, no. 6, Dec. 2022, pp. 2532-6, doi:10.18517/ijaseit.12.6.16596.
Cancer is one of the most common causes of death in the globe. The development of new cancer medicines and the identification of new therapeutic targets is still a pressing necessity. The protein AKR1B10 was discovered to be a valuable biomarker for the diagnosis and prognosis of some malignancies. Over expression of the AKR1B10 gene is found in lung cancer, oral squamous cell carcinoma, breast cancer, cholangiocarcinoma, pancreatic cancer and liver cancer. AKR1B10 is implicated in detoxification, retinoic acid metabolism, and lipid synthesis, among other pathological actions. AKR1B10 is known to be carcinogenic and can be utilized as a tumor marker, according to research. The tetraprenyltoluquinone compound is an isolate from the bark of kandis (Garcinia cowa, Roxb) which has been reported to have anticancer activity in vivo and in vitro and has the potential to be developed as an anticancer drug derived from natural ingredients. This study aims to determine the activity of the tetraprenyltoluquinone compound in silico with the target of the AKR1B10 protein. The method used is molecular docking using PLANTS (Protein Ligand ANT System) for protein visualization and preparation and Ligplus program for visualizing amino acids. The docking score results showed that the AKR1B10 protein interaction with the test ligand tetraprenyltoluquinone is lower than the native ligand, which means the binding energy of tetraprenyltoluquinone to the AKR1B10 (PDB ID: 1ZUA) protein was higher than the native ligand tolrestat. These results indicate that tetraprenyltoluquinone is a potential inhibitor of the AKR1B10 protein in the pathway of cancer.

J. Shi, L. Chen, Y. Chen, Y. Lu, X. Chen, and Z. Yang, "Aldo-Keto reductase family 1 member B10 (AKR1B10) overexpression in tumors predicts worse overall survival in hepatocellular carcinoma," J Cancer, vol. 10, no. 20, 2019, doi: 10.7150/jca.32768.

X. Ye et al., "A Large-Scale Multicenter Study Validates Aldo-Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma," Hepatology, vol. 69, no. 6, 2019, doi: 10.1002/hep.30519.

Z. Cao et al., “AKR1B10 as a Potential Novel Serum Biomarker for Breast Cancer: A Pilot Study,” Frontiers in Oncology, vol. 12, 2022, doi: 10.3389/fonc.2022.727505.

S. Banerjee, "Aldo Keto Reductases AKR1B1 and AKR1B10 in Cancer: Molecular Mechanisms and Signaling Networks," 2021. doi: 10.1007/5584_2021_634.

K. Fan, Z. Liu, M. Gao, K. Tu, Q. Xu, and Y. Zhang, "Targeting Nutrient Dependency in Cancer Treatment," Frontiers in Oncology, vol. 12. 2022. doi: 10.3389/fonc.2022.820173.

W. Wang, C. Yang, T. Wang, and H. Deng, "Complex roles of nicotinamide N-methyltransferase in cancer progression," Cell Death and Disease, vol. 13, no. 3. 2022. doi: 10.1038/s41419-022-04713-z.

T. M. Penning, S. Jonnalagadda, P. C. Trippier, and T. L. Rižner, "Aldo-keto reductases and cancer drug resistance," Pharmacological Reviews, vol. 73, no. 3, 2021, doi: 10.1124/pharmrev.120.000122.

K. Yamamoto and S. Endo, "Bombyx mori-derived aldo-keto reductase AKR2E8 detoxifies aldehydes present in mulberry leaves," Chemico-Biological Interactions, vol. 351, 2022, doi: 10.1016/j.cbi.2021.109717.

F. Balestri, R. Moschini, U. Mura, M. Cappiello, and A. del Corso, "In Search of Differential Inhibitors of Aldose Reductase," Biomolecules, vol. 12, no. 4. 2022. doi: 10.3390/biom12040485.

S. Endo, T. Matsunaga, and T. Nishinaka, "The role of akr1b10 in physiology and pathophysiology," Metabolites, vol. 11, no. 6. 2021. doi: 10.3390/metabo11060332.

K. Amai et al., "Quantitative analysis of mRNA expression levels of aldo-keto reductase and short-chain dehydrogenase/reductase isoforms in human livers," Drug Metabolism and Pharmacokinetics, vol. 35, no. 6, 2020, doi: 10.1016/j.dmpk.2020.08.004.

R. Liu et al., "Prognostic value of aldo-keto reductase family 1 member B10 (AKR1B10) in digestive system cancers: A meta-analysis," Medicine, vol. 100, no. 14, 2021, doi: 10.1097/MD.0000000000025454.

M. Hojnik, S. Frković Grazio, I. Verdenik, and T. L. Rižner, "Akr1b1 and akr1b10 as prognostic biomarkers of endometrioid endometrial carcinomas," Cancers (Basel), vol. 13, no. 14, 2021, doi: 10.3390/cancers13143398.

F. S. Wahyuni et al., "A new ring-reduced tetraprenyltoluquinone and a prenylated xanthone from Garcinia cowa," Australian Journal of Chemistry, 2004, doi: 10.1071/CH03175.

F. S. Wahyuni, L. S. Hui, J. Stanslas, N. H. J. Lajis, and Dachriyanus, "In vivo study of tetraprenyltoluquinone, an anticancer compound from garcinia cowa roxb," Journal of Young Pharmacists, 2017, doi: 10.5530/jyp.2017.9.58.

F. S. Wahyuni, J. Stanslas, N. H. Lajis, and Dachriyanus, "Cytotoxicity studies of tetraprelyltoluquinone, a prenilated hydroquinone from Garcina cowa Roxb on H-460, MCF-7 and DU-145," International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 3, pp. 60-63, 2015.

F. S. Wahyuni, K. Shaari, J. Stanslas, N. H. Lajis, and Dachriyanus, "Cytotoxic Xanthones from the Stem Bark of Garcinia cowa Roxb," Journal of Chemical and Pharmaceutical Research, vol. 7, no. 1, pp. 227-236, 2015.

H. Chikhale, "Review on In-silico Techniques an Approach to Drug Discovery," Current Trends in Pharmacy and Pharmaceutical Chemistry, vol. 2, no. 1, 2020.

A. Devi, "In silico Designing of Novel Inhibitors for Triple Inhibition of Aldose Reductase, Aldose Reductase Like Protein 1, and Aldehyde Reductase," Current Computer-Aided Drug Design, vol. 16, no. 6, 2019, doi: 10.2174/1573409915666191015111200.

J. Liu, H. Ban, Y. Liu, and J. Ni, "The expression and significance of AKR1B10 in laryngeal squamous cell carcinoma," Scientific Reports, vol. 11, no. 1, 2021, doi: 10.1038/s41598-021-97648-y.

D. Serlahwaty and C. Giovani, "In silico screening of mint leaves compound (Mentha piperita L.) as a potential inhibitor of SARS-CoV-2," Pharmacy Education, vol. 21, no. 2, 2021, doi: 10.46542/pe.2021.212.8186.

G. Nugraha and E. P. Istyastono, "Virtual target construction for structure-based screening in the discovery of histamine h2 receptor ligands," International Journal of Applied Pharmaceutics, vol. 13, no. 3, 2021, doi: 10.22159/ijap.2021v13i3.41202.

L. R. de Souza Neto et al., “In silico Strategies to Support Fragment-to-Lead Optimization in Drug Discovery,” Frontiers in Chemistry, vol. 8. 2020. doi: 10.3389/fchem.2020.00093.

J. Du et al., "New techniques and strategies in drug discovery," Chinese Chemical Letters, vol. 31, no. 7, 2020, doi: 10.1016/j.cclet.2020.03.028.

P. A. Greenidge, C. Kramer, J. C. Mozziconacci, and W. Sherman, "Improving docking results via reranking of ensembles of ligand poses in multiple X-ray protein conformations with MM-GBSA," Journal of Chemical Information and Modeling, vol. 54, no. 10, 2014, doi: 10.1021/ci5003735.

K. Liu and H. Kokubo, "Prediction of ligand binding mode among multiple cross-docking poses by molecular dynamics simulations," Journal of Computer-Aided Molecular Design, vol. 34, no. 11, 2020, doi: 10.1007/s10822-020-00340-y.

C. Zhang et al., "Tolrestat acts atypically as a competitive inhibitor of the thermostable aldo-keto reductase Tm1743 from Thermotoga maritima," FEBS Letters, vol. 594, no. 3, 2020, doi: 10.1002/1873-3468.13630.

A. S. Grewal, K. Thapa, N. Kanojia, N. Sharma, and S. Singh, "Natural Compounds as Source of Aldose Reductase (AR) Inhibitors for the Treatment of Diabetic Complications: A Mini Review," Current Drug Metabolism, vol. 21, no. 14, 2020, doi: 10.2174/1389200221666201016124125.

J. Sharma, V. Kumar Bhardwaj, R. Singh, V. Rajendran, R. Purohit, and S. Kumar, "An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against nonstructural protein-15 of SARS-CoV-2," Food Chemistry, vol. 346, 2021, doi: 10.1016/j.foodchem.2020.128933.

C. Norn et al., "Protein sequence design by conformational landscape optimization," Proc Natl Acad Sci U S A, vol. 118, no. 11, 2021, doi: 10.1073/PNAS.2017228118.

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