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Abstract

Background

Prostate cancer remains the second most common cancer among men around the world, with 1.4 million new cases annually. Treatment resistance and off-target toxicity require innovative therapeutic approaches. Natural compounds such as eugenol exhibit anticancer potential, but poor pharmacokinetic properties constrain clinical application.

Objective

This study evaluated the cytotoxic, apoptotic, and pharmacokinetic properties of three eugenol-derived allyl phenol compounds (38, 42, 47), previously recognized as potent 15-lipoxygenase-1 (15-LOX-1) inhibitors, in prostate cancer models.

Methods

The cytotoxic activity was evaluated in PC-3 prostate cancer cells and Human Dermal Fibroblasts (HDF) using AlamarBlue assays, flow cytometry, and morphological analysis. Computational validation involved Density Functional Theory (DFT) calculations, molecular docking into 15-lipoxygenase-1 (15-LOX-1; PDB: 2P0M), and structural analysis. Pharmacokinetic and toxicity profiles were predicted using SwissADME, pkCSM, and ProTox-III platforms.

Results

All three compounds were cytotoxic to PC-3 cells in a concentration-dependent way with some selectivity for normal cells. Apoptosis was confirmed by increased sub-G1 peak and morphological changes, while BAX or BCL-2 mRNA levels did not change. studies (DFT and docking) showed that the compounds bound well to 15-LOX-1 (docking scores: -6.6 to -7.3 kcal/mol), with compound 42 having the strongest binding affinity. Structural analysis showed that the proteins were moderately flexible (B-factor: 47.45 ± 13.07 Ų), which supports stable ligand accommodation. Computational ADME/toxicity predictions suggested generally favorable pharmacokinetic profiles; however, compound 42 was poorly soluble, and compound 47 was identified as a P-gp substrate, indicating a potential efflux liability.

Discussion

The pro-apoptotic effects observed despite unaltered BAX and BCL-2 mRNA levels indicate that the apoptotic response is likely mediated through mechanisms other than transcriptional regulation of these genes, potentially by blocking 15-LOX-1. Computational modeling indicated that all three compounds can effectively bind to the 15-LOX-1 active site, and their binding affinities are in line with their experimental inhibitory potencies (IC: 0.80–0.88 µM). The integration of and results confirms the therapeutic potential of these compounds and underscores the necessity for additional mechanistic studies and evaluation.

Conclusion

These results highlight the anticancer properties of eugenol-derived allylphenol compounds. The compounds induce apoptosis by mechanisms independent of BAX/BCL-2 transcriptional modulation. Computational modeling suggests potential involvement of 15-LOX-1; nevertheless, direct mechanistic validation caspase activity, ROS generation, or protein-level quantification of BAX/BCL-2 is necessary to verify the apoptotic pathway. The compounds suggest favorable pharmacokinetic profiles along with strong enzyme binding characteristics. Compound 38 exhibited the most balanced profile, characterized by high cytotoxicity, selectivity, and predicted ADME properties. Additional mechanistic investigations and validation are necessary to advance these candidates through preclinical development.

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2026-04-03
2026-04-17

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References

  1. Olko P. Licak G. Tomkiewicz J. Tomkiewicz M. Paluch M. Sałata P. Żuchnik M. Radulski J. Szczuraszek H. Bętkowska P. Dadziak M. The influence of genetic and environmental factors on the incidence of prostate cancer in men. J. Educ. Health Sport 2023 13 3 271 282 10.12775/JEHS.2023.13.03.036
    [Google Scholar]
  2. Siegel R.L. Kratzer T.B. Giaquinto A.N. Sung H. Jemal A. Cancer statistics, 2025. CA Cancer J. Clin. 2025 75 1 10 45 10.3322/caac.21871 39817679
    [Google Scholar]
  3. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  4. Turco F. Gillessen S. Herrmann K. Paone G. Omlin A. Treatment landscape of prostate cancer in the era of PSMA radiopharmaceutical therapy. J. Nucl. Med. 2025 66 5 665 672 10.2967/jnumed.124.267730 40015917
    [Google Scholar]
  5. Liu W.H. Yao J.T. Ye S.J. Hu P.C. Fei X. Ma Q. Chen H.C. Recent progress and controversies in the treatment of metastatic hormone-sensitive prostate cancer. J. Men’s Health 2024 20 6 1 7 10.22514/jomh.2024.083
    [Google Scholar]
  6. Che J. Liu Y. Liu Y. Song J. Cui H. Feng D. Tian A. Zhang Z. Xu Y. The application of emerging immunotherapy in the treatment of prostate cancer: Progress, dilemma and promise. Front. Immunol. 2025 16 1544882 10.3389/fimmu.2025.1544882 40145100
    [Google Scholar]
  7. Kwon W.A. Joung J.Y. Immunotherapy in prostate cancer: From a “cold” tumor to a “hot” prospect. Cancers 2025 17 7 1064 10.3390/cancers17071064 40227610
    [Google Scholar]
  8. Sekhoacha M. Riet K. Motloung P. Gumenku L. Adegoke A. Mashele S. Prostate cancer review: Genetics, diagnosis, treatment options, and alternative approaches. Molecules 2022 27 17 5730 10.3390/molecules27175730 36080493
    [Google Scholar]
  9. Kubatka P. Kello M. Kajo K. Samec M. Jasek K. Vybohova D. Uramova S. Liskova A. Sadlonova V. Koklesova L. Murin R. Adamkov M. Smejkal K. Svajdlenka E. Solar P. Samuel S.M. Kassayova M. Kwon T.K. Zubor P. Pec M. Danko J. Büsselberg D. Mojzis J. Chemopreventive and therapeutic efficacy of Cinnamomum zeylanicum L. bark in experimental breast carcinoma: Mechanistic in vivo and in vitro analyses. Molecules 2020 25 6 1399 10.3390/molecules25061399 32204409
    [Google Scholar]
  10. Slameňová D. Horváthová E. Wsólová L. Šramková M. Navarová J. Investigation of anti-oxidative, cytotoxic, DNA-damaging and DNA-protective effects of plant volatiles eugenol and borneol in human-derived HepG2, Caco-2 and VH10 cell lines. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2009 677 1-2 46 52 10.1016/j.mrgentox.2009.05.016 19501671
    [Google Scholar]
  11. Jaganathan S.K. Supriyanto E. Antiproliferative and molecular mechanism of eugenol-induced apoptosis in cancer cells. Molecules 2012 17 6 6290 6304 10.3390/molecules17066290 22634840
    [Google Scholar]
  12. Huang M. Lu J.J. Ding J. Natural products in cancer therapy: Past, present and future. Nat. Prod. Bioprospect. 2021 11 1 5 13 10.1007/s13659‑020‑00293‑7 33389713
    [Google Scholar]
  13. Zari A.T. Zari T.A. Hakeem K.R. Anticancer properties of eugenol: A review. Molecules 2021 26 23 7407 10.3390/molecules26237407 34885992
    [Google Scholar]
  14. Pramod K. Ansari S.H. Ali J. Eugenol: a natural compound with versatile pharmacological actions. Nat. Prod. Commun. 2010 5 12 1934578X1000501236 10.1177/1934578X1000501236 21299140
    [Google Scholar]
  15. Ulanowska M. Olas B. Biological properties and prospects for the application of eugenol—A review. Int. J. Mol. Sci. 2021 22 7 3671 10.3390/ijms22073671 33916044
    [Google Scholar]
  16. Nisar M.F. Khadim M. Rafiq M. Chen J. Yang Y. Wan C.C. Pharmacological properties and health benefits of eugenol: A comprehensive review. Oxid. Med. Cell. Longev. 2021 2021 1 2497354 10.1155/2021/2497354 34394824
    [Google Scholar]
  17. Yi J.L. Shi S. Shen Y.L. Wang L. Chen H.Y. Zhu J. Ding Y. Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines. Int. J. Clin. Exp. Pathol. 2015 8 2 1116 1127 25972998
    [Google Scholar]
  18. Cassano R. Cuconato M. Calviello G. Serini S. Trombino S. Recent advances in nanotechnology for the treatment of melanoma. Molecules 2021 26 4 785 10.3390/molecules26040785 33546290
    [Google Scholar]
  19. Sun X. Veeraraghavan V.P. Surapaneni K.M. Hussain S. Mathanmohun M. Alharbi S.A. Aladresi A.A.M. Chinnathambi A. Eugenol–piperine loaded polyhydroxy butyrate/polyethylene glycol nanocomposite‐induced apoptosis and cell death in nasopharyngeal cancer (C666‐1) cells through the inhibition of the PI3K/AKT/mTOR signaling pathway. J. Biochem. Mol. Toxicol. 2021 35 4 e22700 10.1002/jbt.22700 33421271
    [Google Scholar]
  20. Padhy I. Paul P. Sharma T. Banerjee S. Mondal A. Molecular mechanisms of action of eugenol in cancer: Recent trends and advancement. Life 2022 12 11 1795 10.3390/life12111795 36362950
    [Google Scholar]
  21. Nazreen S. Elbehairi S.E.I. Malebari A.M. Alghamdi N. Alshehri R.F. Shati A.A. Ali N.M. Alfaifi M.Y. Elhenawy A.A. Alam M.M. New natural eugenol derivatives as antiproliferative agents: Synthesis, biological evaluation, and computational studies. ACS Omega 2023 8 21 18811 18822 10.1021/acsomega.3c00933 37273621
    [Google Scholar]
  22. Aghasizadeh M. Moghaddam T. Bahrami A.R. Sadeghian H. Alavi S.J. Kazemi T. Matin M.M. Evaluation of several farnesyloxycarbostyril derivatives as potential 15-LOX-1 inhibitors for prostate cancer treatment. Toxicol. Appl. Pharmacol. 2025 498 117293 10.1016/j.taap.2025.117293 40057000
    [Google Scholar]
  23. Uma Maheswari P. Muthappa R. Bindhya K.P. Meera Sheriffa Begum K.M. Evaluation of folic acid functionalized BSA-CaFe2O4 nanohybrid carrier for the controlled delivery of natural cytotoxic drugs hesperidin and eugenol. J. Drug Deliv. Sci. Technol. 2021 61 102105 10.1016/j.jddst.2020.102105
    [Google Scholar]
  24. Danova K. Petreska Stanoeva J. Stoyanova E. Alipieva K. Stefova M. Aneva I. Lipoxygenase inhibitory activity and prostate cancer cytotoxicity of in situ- and in vitro-cultivated balkan endemic Sideritis scardica Griseb. Plants 2025 14 21 3263 10.3390/plants14213263 41225814
    [Google Scholar]
  25. Li X. Mao J. Research progress on the role of lipoxygenase and its inhibitors in prostate cancer. Future Oncol. 2024 20 40 3549 3568 10.1080/14796694.2024.2419356 39535136
    [Google Scholar]
  26. Kazan H.H. Özketen A.Ç. Mamatoğlu Ç.U. Cyclooxygenases and lipoxygenases in cancer drug resistance. Gazi Medical Journal 2025 36 3 376 384 10.12996/gmj.2025.4388
    [Google Scholar]
  27. Alavi S.J. Seyedi S.M. Saberi S. Safdari H. Eshghi H. Sadeghian H. Allylphenols as a new class of human 15‐lipoxygenase‐1 inhibitors. Drug Dev. Res. 2021 82 2 259 266 10.1002/ddr.21749 33022099
    [Google Scholar]
  28. Zhao H Ma TF Lin J Liu LL Sun WJ Guo LX Wang SQ Otecko NO Zhang YP Identification of valid reference genes for mRNA and microRNA normalisation in prostate cancer cell lines. Sci. Rep. 2018 8 1 1949 10.1038/s41598‑018‑19458‑z 29386530
    [Google Scholar]
  29. Talebian S. Shahnavaz B. Shakiba M. Rassouli F.B. Illuminating new possibilities: Effects of copper oxide nanoparticles on gastrointestinal adenocarcinoma cells in hypoxic condition. Heliyon 2024 10 10 e31414 10.1016/j.heliyon.2024.e31414 38813193
    [Google Scholar]
  30. 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 1 42717 10.1038/srep42717 28256516
    [Google Scholar]
  31. Pires D.E.V. Blundell T.L. Ascher D.B. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J. Med. Chem. 2015 58 9 4066 4072 10.1021/acs.jmedchem.5b00104 25860834
    [Google Scholar]
  32. Kandsi F. Lafdil F.Z. Elbouzidi A. Bouknana S. Miry A. Addi M. Conte R. Hano C. Gseyra N. Evaluation of acute and subacute toxicity and LC-MS/MS compositional alkaloid determination of the hydroethanolic extract of Dysphania ambrosioides (L.) mosyakin and clemants flowers. Toxins 2022 14 7 475 10.3390/toxins14070475 35878213
    [Google Scholar]
  33. Banerjee P. Kemmler E. Dunkel M. Preissner R. ProTox 3.0: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024 52 W513 W520 10.1093/nar/gkae303
    [Google Scholar]
  34. Neese F. Software update: The ORCA program system—version 6.0. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2025 15 2 e70019 10.1002/wcms.70019
    [Google Scholar]
  35. Trott O. Olson A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 2010 31 2 455 461 10.1002/jcc.21334 19499576
    [Google Scholar]
  36. Eberhardt J. Santos-Martins D. Tillack A.F. Forli S. AutoDock Vina 1.2. 0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model. 2021 61 8 3891 3898 10.1021/acs.jcim.1c00203 34278794
    [Google Scholar]
  37. Ghosh R. Ganapathy M. Alworth W.L. Chan D.C. Kumar A.P. Combination of 2-methoxyestradiol (2-ME2) and eugenol for apoptosis induction synergistically in androgen independent prostate cancer cells. J. Steroid Biochem. Mol. Biol. 2009 113 1-2 25 35 10.1016/j.jsbmb.2008.11.002 19084597
    [Google Scholar]
  38. Youle R.J. Strasser A. The BCL-2 protein family: Opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 2008 9 1 47 59 10.1038/nrm2308 18097445
    [Google Scholar]
  39. Waring M.J. Arrowsmith J. Leach A.R. Leeson P.D. Mandrell S. Owen R.M. Pairaudeau G. Pennie W.D. Pickett S.D. Wang J. Wallace O. Weir A. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat. Rev. Drug Discov. 2015 14 7 475 486 10.1038/nrd4609 26091267
    [Google Scholar]
  40. Han C. Wang B. Factors that impact the developability of drug candidates: An overview. Drug Delivery: Principles and Applications. Canada John Wiley & Sons, Inc. 2005 1 14 10.1002/0471475734.ch1
    [Google Scholar]
  41. Aungst B.J. Optimizing oral bioavailability in drug discovery: An overview of design and testing strategies and formulation options. J Pharm Sci. 2017 106 4 921 929 10.1016/j.xphs.2016.12.002 27986598
    [Google Scholar]
  42. Lipinski C.A. Lombardo F. Dominy B.W. Feeney P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2001 46 1-3 3 26 10.1016/S0169‑409X(00)00129‑0 11259830
    [Google Scholar]
  43. Ghose A.K. Viswanadhan V.N. Wendoloski J.J. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J. Comb. Chem. 1999 1 1 55 68 10.1021/cc9800071 10746014
    [Google Scholar]
  44. Veber D.F. Johnson S.R. Cheng H.Y. Smith B.R. Ward K.W. Kopple K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002 45 12 2615 2623 10.1021/jm020017n 12036371
    [Google Scholar]
  45. Egan W.J. Merz K.M. Jr Baldwin J.J. Prediction of drug absorption using multivariate statistics. J. Med. Chem. 2000 43 21 3867 3877 10.1021/jm000292e 11052792
    [Google Scholar]
  46. Hubatsch I. Ragnarsson E.G.E. Artursson P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat. Protoc. 2007 2 9 2111 2119 10.1038/nprot.2007.303 17853866
    [Google Scholar]
  47. Kus M. Ibragimow I. Piotrowska-Kempisty H. Caco-2 cell line standardization with pharmaceutical requirements and in vitro model suitability for permeability assays. Pharmaceutics. 2023 15 11 2523 10.3390/pharmaceutics15112523 38004503
    [Google Scholar]
  48. Pérez M.A.C. Sanz M.B. Torres L.R. Ávalos R.G. González M.P. Díaz H.G. A topological sub-structural approach for predicting human intestinal absorption of drugs. Eur. J. Med. Chem. 2004 39 11 905 916 10.1016/j.ejmech.2004.06.012 15501539
    [Google Scholar]
  49. Ambudkar S.V. Kimchi-Sarfaty C. Sauna Z.E. Gottesman M.M. P-glycoprotein: From genomics to mechanism. Oncogene 2003 22 47 7468 7485 10.1038/sj.onc.1206948 14576852
    [Google Scholar]
  50. Mandal S.K. Muzaffar-Ur-Rehman M. Puri S. Sharma P.K. Murugesan S. Deepa P.R. In silico and in vitro investigations reveal pan-PPAR agonist activity and anti-NAFLD efficacy of polydatin by modulating hepatic lipid-energy metabolism. Sci. Rep. 2025 15 1 26995 10.1038/s41598‑025‑12357‑0 40707685
    [Google Scholar]
  51. Urzì Brancati V. Scarpignato C. Minutoli L. Pallio G. Use of pharmacogenetics to optimize immunosuppressant therapy in kidney-transplanted patients. Biomedicines 2022 10 8 1798 10.3390/biomedicines10081798 35892699
    [Google Scholar]
  52. Yin J. Wang J. Renal drug transporters and their significance in drug–drug interactions. Acta Pharm. Sin. B 2016 6 5 363 373 10.1016/j.apsb.2016.07.013 27709005
    [Google Scholar]
  53. Sahota T. Danhof M. Della Pasqua O. Pharmacology-based toxicity assessment: Towards quantitative risk prediction in humans. Mutagenesis 2016 31 3 359 374 10.1093/mutage/gev081 26970519
    [Google Scholar]
  54. Seal S. Mahale M. García-Ortegón M. Joshi C.K. Hosseini-Gerami L. Beatson A. Greenig M. Shekhar M. Patra A. Weis C. Mehrjou A. Badré A. Paisley B. Lowe R. Singh S. Shah F. Johannesson B. Williams D. Rouquie D. Clevert D.A. Schwab P. Richmond N. Nicolaou C.A. Gonzalez R.J. Naven R. Schramm C. Vidler L.R. Mansouri K. Walters W.P. Wilk D.D. Spjuth O. Carpenter A.E. Bender A. Machine learning for toxicity prediction using chemical structures: Pillars for success in the real world. Chem. Res. Toxicol. 2025 38 5 759 807 10.1021/acs.chemrestox.5c00033 40314361
    [Google Scholar]
  55. Fares J. Fares M.Y. Khachfe H.H. Salhab H.A. Fares Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct. Target. Ther. 2020 5 1 28 10.1038/s41392‑020‑0134‑x 32296047
    [Google Scholar]
  56. Poon D.M.C. Cheung W.S.K. Chiu P.K.F. Chung D.H.S. Kung J.B.T. Lam D.C.M. Leung A.K.C. Ng A.C.F. O’Sullivan J.M. Teoh J.Y.C. Wu P.Y. Wu S.K.K. Kwong P.W.K. Treatment of metastatic castration-resistant prostate cancer: Review of current evidence and synthesis of expert opinions on radioligand therapy. Front. Oncol. 2025 15 1530580 10.3389/fonc.2025.1530580 40071082
    [Google Scholar]
  57. Ghanbari-Movahed M. Kaceli T. Mondal A. Farzaei M.H. Bishayee A. Recent advances in improved anticancer efficacies of camptothecin nano-formulations: A systematic review. Biomedicines 2021 9 5 480 10.3390/biomedicines9050480 33925750
    [Google Scholar]
  58. Liu B. Zhou H. Tan L. Siu K.T.H. Guan X.Y. Exploring treatment options in cancer: Tumor treatment strategies. Signal Transduct. Target. Ther. 2024 9 1 175 10.1038/s41392‑024‑01856‑7 39013849
    [Google Scholar]
  59. Xiao J. Zhang M. Wu D. Side effects of prostate cancer therapies and potential management. J. Biol. Methods 2024 11 3 e99010018 10.14440/jbm.2024.0019 39544189
    [Google Scholar]
  60. Newman D.J. Cragg G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 2020 83 3 770 803 10.1021/acs.jnatprod.9b01285 32162523
    [Google Scholar]
  61. Al-Kharashi L.A. Bakheet T. AlHarbi W.A. Al-Moghrabi N. Aboussekhra A. Eugenol modulates genomic methylation and inactivates breast cancer‐associated fibroblasts through E2F1‐dependent downregulation of DNMT1/DNMT3A. Mol. Carcinog. 2021 60 11 784 795 10.1002/mc.23344 34473867
    [Google Scholar]
  62. Jaganathan S.K. Mazumdar A. Mondhe D. Mandal M. Apoptotic effect of eugenol in human colon cancer cell lines. Cell Biol. Int. 2011 35 6 607 615 10.1042/CBI20100118 21044050
    [Google Scholar]
  63. Zaky M.Y. Morsy H.M. Abdel-Moneim A. Zoheir K.M.A. Bragoli A. Abdel-Maksoud M.A. Alamri A. Ahmed O.M. Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms. Discov. Oncol. 2025 16 1 1080 10.1007/s12672‑025‑02243‑6 40506614
    [Google Scholar]
  64. Cui D. Zhang C. Zhang L. Zheng J. Wang J. He L. Jin H. Kang Q. Zhang Y. Li N. Sun Z. Zheng W. Wei J. Zhang S. Feng Y. Tan W. Zhong Z. Natural anti-cancer products: Insights from herbal medicine. Chin. Med. 2025 20 1 82 10.1186/s13020‑025‑01124‑y 40490812
    [Google Scholar]
  65. Gupta S.C. Kismali G. Aggarwal B.B. Curcumin, a component of turmeric: From farm to pharmacy. Biofactors 2013 39 1 2 13 10.1002/biof.1079 23339055
    [Google Scholar]
  66. Sihombing I.N.N. Arsianti A. Network pharmacology prediction and molecular docking analysis on the mechanism of eugenol as a candidate against estrogen receptor-positive breast cancer. J. Pharm. Pharmacogn. Res. 2024 12 5 837 851 10.56499/jppres23.1699_12.5.837
    [Google Scholar]
  67. Wijewantha N. Sane S. Eikanger M. Antony R.M. Potts R.A. Lang L. Rezvani K. Sereda G. Enhancing anti-tumorigenic efficacy of eugenol in human colon cancer cells using enzyme-responsive nanoparticles. Cancers 2023 15 4 1145 10.3390/cancers15041145 36831488
    [Google Scholar]
  68. Liu X. Nie Y. Liu Y. Chen M. Cardiovascular protective properties of the natural product eugenol. Eur. J. Pharmacol. 2025 1003 177929 10.1016/j.ejphar.2025.177929 40623537
    [Google Scholar]
  69. Taylor R.C. Cullen S.P. Martin S.J. Apoptosis: Controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 2008 9 3 231 241 10.1038/nrm2312 18073771
    [Google Scholar]
  70. Kuhn H. Banthiya S. van Leyen K. Mammalian lipoxygenases and their biological relevance. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2015 1851 4 308 330 10.1016/j.bbalip.2014.10.002 25316652
    [Google Scholar]
  71. Brash A.R. Lipoxygenases: Occurrence, functions, catalysis, and acquisition of substrate. J. Biol. Chem. 1999 274 34 23679 23682 10.1074/jbc.274.34.23679 10446122
    [Google Scholar]
  72. Abdullah M.L. Al-Shabanah O. Hassan Z.K. Hafez M.M. Eugenol-induced autophagy and apoptosis in breast cancer cells via PI3K/AKT/FOXO3a pathway inhibition. Int. J. Mol. Sci. 2021 22 17 9243 10.3390/ijms22179243 34502165
    [Google Scholar]
  73. Green D.R. Llambi F. Cell death signaling. Cold Spring Harb. Perspect. Biol. 2015 7 12 a006080 10.1101/cshperspect.a006080 26626938
    [Google Scholar]
  74. Ancuceanu R. Lascu B.E. Drăgănescu D. Dinu M. In silico ADME methods used in the evaluation of natural products. Pharmaceutics 2025 17 8 1002 10.3390/pharmaceutics17081002 40871023
    [Google Scholar]
  75. Azzam KA SwissADME and pkCSM webservers predictors: An integrated online platform for accurate and comprehensive predictions for in silico ADME/T properties of artemisinin and its derivatives. Complex Use Miner. Resour. 2023 325 2 14 21 10.31643/2023/6445.13
    [Google Scholar]
  76. Rao Gajula S.N. Reddy G.N. Reddy D.S. Sonti R. Pharmacokinetic drug-drug interactions: An insight into recent US FDA-approved drugs for prostate cancer. Bioanalysis 2020 12 22 1647 1664 10.4155/bio‑2020‑0242 33156691
    [Google Scholar]
  77. Lim J.S.L. Chen X.A. Singh O. Yap Y.S. Ng R.C.H. Wong N.S. Wong M. Lee E.J.D. Chowbay B. Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients. Br. J. Clin. Pharmacol. 2011 71 5 737 750 10.1111/j.1365‑2125.2011.03905.x 21480951
    [Google Scholar]
  78. Nadendla R. Molecular modification: A strategy in drug discovery and drug design. Biomed. J. Sci. Tech. Res. 2023 52 2 43511 43522 10.26717/BJSTR.2023.52.008220
    [Google Scholar]
  79. Conrad J. Vaz R.J. Validating the use of rational modification of compounds to reduce P-gp efflux. Arch. Pharmacol. Ther. 2024 6 1 34 39 10.33696/Pharmacol.6.054
    [Google Scholar]
  80. Ong H.W. Yang X. Smith J.L. Taft-Benz S. Howell S. Dickmander R.J. Havener T.M. Sanders M.K. Brown J.W. Couñago R.M. Chang E. Krämer A. Moorman N.J. Heise M. Axtman A.D. Drewry D.H. Willson T.M. Strategic fluorination to achieve a potent, selective, metabolically stable, and orally bioavailable inhibitor of CSNK2. Molecules 2024 29 17 4158 10.3390/molecules29174158 39275006
    [Google Scholar]
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Anticancer and Drug-Likeness Evaluation of Allylphenol-Based 15-LOX Inhibitors in Prostate Cancer: An In Vitro and Computational Study
Bentham Science Publishers ; https://doi.org/10.2174/0118715206430349260204105940
/content/journals/acamc/10.2174/0118715206430349260204105940
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  • Article Type:     Research Article
Keywords: anticancer properties ; DFT ; allyl phenols ; eugenol derivatives ; Prostate cancer ; 15-LOX inhibitors

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