Synthesis, Molecular Docking, Characterization, and Preliminary Evaluation of Some New 1, 3-Diazetidin-2-One Derivatives as Anticancer Agents

Authors

  • farah haidar Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
  • Monther Faisal Mahdi Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.
  • Ayad Kareem Khan Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.

DOI:

https://doi.org/10.32947/ajps.v24i1.1026

Keywords:

1,3-diazetidin-2-one, Docking Study, Lung Cancer

Abstract

A series of novel 1,3-diazetidin-2-one derivatives were designed, synthesized, and evaluated preliminary (In Vitro) for their cytotoxic activity against the lung (A549) cancer cell line. GOLD software (version 2021.2.0) was used to conduct a molecular docking study;

the tested derivatives demonstrated significant anticancer activity compared to the reference drug (erlotinib). PLP-fitness values for the final compounds are 79.81, 80.80, and 81.57, respectively, whereas the reference ligand, erlotinib, had a value of 76.20. The synthesized compounds were identified and characterized using physicochemical parameters (melting points and Rf values), FTIR, 1H-NMR, and 13C-NMR spectroscopy. According to the IC50 values for the synthesized derivatives, compounds N4a and N4b exhibit outstanding anti-proliferative activity with IC50 value of (7.51, 7.68) µM against A549 cell line, compared to erlotinib, which has an IC50 value of (11.5) µM.

 

References

- Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol 2018;15(2):81–94. DOI: https://doi.org/10.1038/nrclinonc.2017.166

- Hainaut P, Plymoth A. Cancer as a metabolic disease. Curr Opin Oncol 2012;24(1):56–7. DOI: https://doi.org/10.1097/CCO.0b013e32834e388a

- Hornberg JJ, Bruggeman FJ, Westerhoff H V., Lankelma J. Cancer: A Systems Biology disease. BioSystems 2006;83(2-3 SPEC. ISS.):81–90. DOI: https://doi.org/10.1016/j.biosystems.2005.05.014

- Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current Challenges in Cancer Treatment. Clin Ther 2016;38(7):1551–66.Available from:http://dx.doi.org/10.1016/j.clinthera.2016.03.026 DOI: https://doi.org/10.1016/j.clinthera.2016.03.026

- Lemjabbar-Alaoui H, Hassan OUI, Yang YW, Buchanan P. Lung cancer: Biology and treatment options. Biochim Biophys Acta - Rev Cancer 2015;1856(2):189–210. DOI: https://doi.org/10.1016/j.bbcan.2015.08.002

- Hurley LH. DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer 2002;2(3):188–200. Available from:https://www.nature.com/articles/nrc749 DOI: https://doi.org/10.1038/nrc749

- Rahim MA, Jan N, Khan S, Shah H, Madni A, Khan A, et al. Recent advancements in stimuli responsive drug delivery platforms for active and passive cancer targeting. Cancers (Basel) 2021;13(4):1–52. DOI: https://doi.org/10.3390/cancers13040670

- Yewale C, Baradia D, Vhora I, Patil S, Misra A. Biomaterials Epidermal growth factor receptor targeting in cancer : A review of trends and strategies. Biomaterials 2013; Available from: http://dx.doi.org/10.1016/j.biomaterials.2013.07.100 DOI: https://doi.org/10.1016/j.biomaterials.2013.07.100

- Cho H soo, Mason K, Ramyar KX, Stanley AM. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. 2003;421(February). DOI: https://doi.org/10.2210/pdb1n8y/pdb

- Abdelgalil AA, Al-Kahtani HM, Al-Jenoobi FI. Erlotinib. Profiles Drug Subst Excip Relat Methodol 2020 ;45:93–117.Availablefrom: https://pubmed.ncbi.nlm.nih.gov/32164971/ DOI: https://doi.org/10.1016/bs.podrm.2019.10.004

- Borik RM, Fawzy NM, Abu-bakr SM, Aly MS. Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin. 2018;1–18. DOI: https://doi.org/10.3390/molecules23061398

- The Importance of Heterocyclic Compounds in Anti-Cancer Drug Design - Drug Discovery World (DDW). Available from: https://www.ddw-online.com/the-importance-of-heterocyclic-compounds-in-anti-cancer-drug-design-1106-201708/

- Suć Sajko J, Jerić I. Synthesis of Nβ-Substituted 1,2-Diazetidin-3-ones by the Ugi Reaction Comprising Chiral α-Hydrazino Acids. J Org Chem 2022;87(11):7076–84. DOI: https://doi.org/10.1021/acs.joc.2c00238

- Mahdi MF, Naser NH, Hammud NH. Synthesis and Preliminary Pharmacological Evaluation of New Naproxen Analogues Having 1, 2, 4-Triazole-3-Thiol. Int J Pharm Pharm Sci 2017;9(7):66. DOI: https://doi.org/10.22159/ijpps.2017v9i7.18273

- Ammar YA, Khalifa MM, Eisa SI, Ismail MMF. New Naproxen Analogs: Synthesis, Docking and Anti-Inflammatory Evaluation. Polycycl Aromat Compd 2022;42(6):3586–605. Available from: https://doi.org/10.1080/10406638.2020.1871037 DOI: https://doi.org/10.1080/10406638.2020.1871037

- Mahdi MF, Al-smaism RF, Mahmood AI. Synthesis , Characterization of Some New 2-Azetidinone Derivatives. 2015;15(2). DOI: https://doi.org/10.32947/ajps.v15i2.167

- Shi Y, Tang B, Yu PW, Tang B, Hao YX, Lei X, et al. Autophagy protects against oxaliplatin-induced cell death via ER stress and ROS in Caco-2 cells. PLoS One 2012; 7(11). Available from: https://pubmed.ncbi.nlm.nih.gov/23226467/ DOI: https://doi.org/10.1371/journal.pone.0051076

- Kaplan A, Akalin Ciftci G, Kutlu HM. The apoptotic and genomic studies on A549 cell line induced by silver nitrate. Tumor Biol 2017;39(4). DOI: https://doi.org/10.1177/1010428317695033

- Abdul-Majeed SZ, Mahdi MF, Al-Mugdadi SFH. Pharmacological Evaluation of New 4, 5-dihydro-1H-Pyrazole-1-yl acetate Derivatives as Anti-inflammatory Agents. Int J Drug Deliv Technol 2022;12(4):1733–41. DOI: https://doi.org/10.25258/ijddt.12.4.40

- Amer M, Mahdi MF, Khan AK, Raauf AMR. Design, Molecular Docking, Synthesis, Preliminary In Silico ADME Studies, and Anti-inflammatory Evaluation of New Oxazole Derivatives. J Pharm Negat Results 2022;13(7):217–28.

- Bickerton GR, Paolini G V., Besnard J, Muresan S, Hopkins AL. Quantifying the chemical beauty of drugs. Nat Chem 2012;4(2):90–8. DOI: https://doi.org/10.1038/nchem.1243

- Hassanzadeh F, Jafari E, Zarabi M, Khodarahmi G, Vaseghi G. Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds. Res Pharm Sci 2020;15(5):454–62. DOI: https://doi.org/10.4103/1735-5362.297848

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Published

2024-01-14

How to Cite

haidar, farah, Faisal Mahdi, M. ., & Kareem Khan, A. . (2024). Synthesis, Molecular Docking, Characterization, and Preliminary Evaluation of Some New 1, 3-Diazetidin-2-One Derivatives as Anticancer Agents. Al Mustansiriyah Journal of Pharmaceutical Sciences, 24(1), 48–58. https://doi.org/10.32947/ajps.v24i1.1026

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Vol. 24 No. 1 (2024): (Volume24,Issue1,Year2024)

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Copyright (c) 2024 farah haidar, Monther Faisal Mahdi, Ayad Kareem Khan

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