Abstract

Aim: To determine the anticancer and antioxidant activity levels of the synthesized heterocyclic molecule named 1-benzyl-1-(2- methyl-3-oxo-3-(p-tolyl)propyl) piperidin-1-ium chloride.

Methods: The molecule 1-benzyl-1-(2-methyl-3-oxo-3-(p-tolyl) propyl)piperidin-1-ium chloride was synthesized solvent-free via microwave synthesis. Piperidine purification involved dichloromethane extraction with 2 M HCl, followed by 5% NaHCO3 and precipitation with n-hexane. Anticancer activity on A549 lung cancer cells was assessed using the MTT assay. Antioxidant activity was evaluated by DPPH and CUPRAC methods at five concentrations (250-15.6 µM), with ascorbic acid as a control.

Results: The heterocyclic molecule dissolved in PBS was tested for anticancer activity on A549 cells at concentrations ranging from 6.25 to 100 µM. Cytotoxicity was highest at 66.90% for 100 µM and decreased to 5.57% at 6.25 µM, with an IC50 of 32.43 µM. In DPPH assays, the absorbance for AscA varied from 1.263±0.057 to 0.675±0.093, while the piperidine molecule ranged from 1.339±0.044 to 1.072±0.120. In CUPRAC assays, AscA absorbance was 0.227±0.052 and 1.768±0.176, and for the piperidine molecule, it was 0.132±0.042 and 0.142±0.031.

Conclusion: Piperidine is considered a saturated heterocyclic ring and possesses a wide range of biological activities. In this study, it was observed that the synthesized piperidine molecule showed limited DPPH radical scavenging activity. It also showed a high level of cytotoxic effect on A549 cancer cells and could be an important molecule for anticancer studies.

Keywords: antioxidant activity, cancer, cytotoxicity, drug synthesis

Copyright and license

How to cite

1.
Sabancılar İ, Aydemir M, Kaya S. Characteristics of the biological activities of the piperidine complex: an anticancer and antioxidant investigation. Northwestern Med J. 2025;5(2):112-21. https://doi.org/10.54307/2025.NWMJ.142

References

  1. Karakan M, Nazlıkul H. Oxidative stress and free radicals effect on the body. Bilimsel Tamamlayıcı Tıp Regülasyon ve Nöral Terapi Dergisi. 2017; 11(2): 7-11.
  2. Karabulut H, Gülay MŞ. Free radicals. Mehmet Akif Ersoy University Journal of Health Sciences Institute. 2016; 4(1): 50-9.
  3. Snezhkina AV, Kudryavtseva AV, Kardymon OL, et al. ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxid Med Cell Longev. 2019; 2019: 6175804. https://doi.org/10.1155/2019/6175804
  4. Gupta D. Methods for determination of antioxidant capacity: A review. Int J Pharm Sci Res. 2015; 6(2): 546-66.
  5. Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D'Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016; 8(4): 603-19. https://doi.org/10.18632/aging.100934
  6. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011; 147(2): 275-92. https://doi.org/10.1016/j.cell.2011.09.024
  7. Bayat Mokhtari R, Homayouni TS, Baluch N, et al. Combination therapy in combating cancer. Oncotarget. 2017; 8(23): 38022-43. https://doi.org/10.18632/oncotarget.16723
  8. Walter FM, Rubin G, Bankhead C, et al. Symptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study. Br J Cancer. 2015; 112(Suppl 1): S6-13. https://doi.org/10.1038/bjc.2015.30
  9. Guan X. Cancer metastases: challenges and opportunities. Acta Pharm Sin B. 2015; 5(5): 402-18. https://doi.org/10.1016/j.apsb.2015.07.005
  10. Ganesh K, Massagué J. Targeting metastatic cancer. Nat Med. 2021; 27(1): 34-44. https://doi.org/10.1038/s41591-020-01195-4
  11. Ashrafi A, Akter Z, Modareszadeh P, et al. Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance. Cancers (Basel). 2022; 14(19): 4562. https://doi.org/10.3390/cancers14194562
  12. Mitra S, Anand U, Jha NK, et al. Anticancer Applications and Pharmacological Properties of Piperidine and Piperine: A Comprehensive Review on Molecular Mechanisms and Therapeutic Perspectives. Front Pharmacol. 2022; 12: 772418. https://doi.org/10.3389/fphar.2021.772418
  13. Manjusha RK, Begum S, Begum A, Bharathi K. Antioxidant potential of piperidine containing compounds - a short review. Asian Journal of Pharmaceutical and Clinical Research. 2018; 11(8): 66-73. https://doi.org/10.22159/ajpcr.2018.v11i8.26536
  14. Haq IU, Imran M, Nadeem M, Tufail T, Gondal TA, Mubarak MS. Piperine: A review of its biological effects. Phytother Res. 2021; 35(2): 680-700. https://doi.org/10.1002/ptr.6855
  15. Frolov NA, Vereshchagin AN. Piperidine Derivatives: Recent Advances in Synthesis and Pharmacological Applications. Int J Mol Sci. 2023; 24(3): 2937. https://doi.org/10.3390/ijms24032937
  16. Trnka J, Blaikie FH, Logan A, Smith RAJ, Murphy MP. Antioxidant properties of MitoTEMPOL and its hydroxylamine. Free Radic Res. 2009; 43(1): 4-12. https://doi.org/10.1080/10715760802582183
  17. Goel P, Alam O, Naim MJ, Nawaz F, Iqbal M, Alam MI. Recent advancement of piperidine moiety in treatment of cancer- A review. Eur J Med Chem. 2018; 157: 480-502. https://doi.org/10.1016/j.ejmech.2018.08.017
  18. Horáková K, Sovcíková A, Seemannová Z, et al. Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants. Free Radic Biol Med. 2001; 30(6): 650-64. https://doi.org/10.1016/s0891-5849(00)00508-6
  19. Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 1986; 89(2): 271-7. https://doi.org/10.1016/0022-1759(86)90368-6
  20. Şahna KÖ. Investigation of the effects of protein hydrolysates obtained from goat milk on MCF-7 breast cancer cells [master's thesis]. Marmara University; 2019.
  21. Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958; 181: 1199-200. https://doi.org/10.1038/1811199a0
  22. Benaka Prasad SB, Vinaya K, Ananda Kumar CS, Swarup S, Rangappa KS. Synthesis and in vitro antiproliferative activity of diphenyl(sulphonylpiperidin-4-yl)methanol derivatives. Med Chem Res. 2010; 19(3): 220-35. https://doi.org/10.1007/s00044-009-9186-8
  23. Bezerra DP, Pessoa C, de Moraes MO, et al. Antiproliferative effects of two amides, piperine and piplartine, from Piper species. Z Naturforsch C J Biosci. 2005; 60(7-8): 539-43. https://doi.org/10.1515/znc-2005-7-805
  24. Vinaya K, Kavitha CV, Chandrappa S, Prasanna DS, Raghavan SC, Rangappa KS. Synthesis and antileukemic activity of novel 4-(3-(piperidin-4-yl) propyl)piperidine derivatives. Chem Biol Drug Des. 2011; 78(4): 622-30. https://doi.org/10.1111/j.1747-0285.2011.01184.x
  25. Lahmidi S, Anouar EH, El Hafi M, et al. Synthesis, structural elucidation, and antioxidant activity of new phenolic derivatives containing piperidine moiety: Experimental and theoretical investigations. J Heterocycl Chem. 2021; 58(6): 1268-77. https://doi.org/10.1002/jhet.4253
  26. Prashanth MK, Revanasiddappa HD, Lokanatha Rai KM, Veeresh B. Synthesis, characterization, antidepressant and antioxidant activity of novel piperamides bearing piperidine and piperazine analogues. Bioorg Med Chem Lett. 2012; 22(23): 7065-70. https://doi.org/10.1016/j.bmcl.2012.09.089
  27. Karaman N, Sıcak Y, Taşkın-Tok T, et al. New piperidine-hydrazone derivatives: Synthesis, biological evaluations and molecular docking studies as AChE and BChE inhibitors. Eur J Med Chem. 2016; 124: 270-83. https://doi.org/10.1016/j.ejmech.2016.08.037