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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Investigating the Synthesis Methods of 3,5-dione Pyrazolidine and 3,5-dione 1-phenylpyrazolidine in the Presence and Absence of Ultrasound Bath and their Anticancer Effects on MCF-7 Breast Cancer Cells

Author(s): Fatemeh Nadipour, Sabah Salahvarzi* and Zeynab Dadgar

Volume 20, Issue 2, 2024

Published on: 04 October, 2023

Article ID: e250823220380 Pages: 6

DOI: 10.2174/1573407219666230825141438

Price: $65

Abstract

Background: Pyrazolidine 5,3-dione derivatives have a wide range of biological and pharmacological activities and play an important role in the sub-structures of various drugs. They also have inhibitory and antimicrobial properties, anti-tumor, anti-inflammatory, analgesic, antituberculosis, anti-hypertensive, anti-cancer, and anti-Alzheimer. The purpose of the current study was to investigate a number of synthesis methods of pyrazolidine-3,5-dione and 1 phenylpyrazolidine- 3,5-dione in the presence and absence of ultrasound bath and their anti-cancer effects on mcf-7 breast cancer cells.

Methods: In this study, pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione were synthesized using hydrazine, phenylhydrazine, and diethyl malonate by different methods. The advantage of this research compared to other studies is the use of different methods (3 methods and each method were performed in two different conditions, toalling 6 methods) for the synthesis of these two derivatives. The effect of two synthesized derivatives on MCF-7 cell line breast cancer cells was also investigated using MTT (methylthiazole tetrazolium) test. IR, 13CNMR, and HNMR spectroscopy methods have also been used to determine the structure of products.

Results: The results of FT-IR and NMR spectrum analysis confirm the synthesized pyrazolidine- 3,5-dione and 1-phenylpyrazolidine-3,5-dione. Based on the results in zero doses (control group) and 10 μM of all Samples after 24 hours, no significant difference in the number of cells was observed. However, the number of cells significantly decreased after treatment with 20 μM dose of both pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione. Also, there was no significant difference in reducing cancer cell proliferation between pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione samples. In addition, treatment of cancer cells with 40 μM of both hydrazine and phenylhydrazine samples after 24 hours caused approximately 50% cell death and reduced the number of cancer cells by approximately half compared to the control group.

Conclusion: According to the results of this study, treatment of cancer cells with a dose of 40 μM in both samples of pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione after 24 hours caused cell death in approximately 50% of cells and the number of cancer cells is almost half that of the control group.

Keywords: MCF-7 breast cancer, pyrazolidine-3, 5-dione, hydrazine, phenylhydrazine, diethyl malonate, chemotherapy drugs.

Graphical Abstract
[1]
Geck, R.C.; Foley, J.R.; Murray Stewart, T.; Asara, J.M.; Casero, R.A., Jr; Toker, A. Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy. J. Biol. Chem., 2020, 295(19), 6263-6277.
[http://dx.doi.org/10.1074/jbc.RA119.012376] [PMID: 32139506]
[2]
Alharbi, A.; Qurban, J.; Abualnaja, M.M.; Abumelha, H.M.; Saad, F.A.; El-Metwaly, N.M.; El-Metwaly, N.M. Molecular modeling and docking studies of new antioxidant pyrazole-thiazole hybrids. J. Mol. Struct., 2022, 1267, 133582.
[http://dx.doi.org/10.1016/j.molstruc.2022.133582]
[3]
Kumar, H.; Jain, S. Synthesis and antimicrobial evaluation of 4-benzylidene-pyrazolidine-3,5-dione derivatives. Int. J. Pharm. Sci. Res., 2013, 4(1), 453-457.
[4]
Yu, B.; Zhao, B.; Hao, Z.; Chen, L.; Cao, L.; Guo, X.; Zhang, N.; Yang, D.; Tang, L.; Fan, Z. Design, synthesis and biological evaluation of pyrazole-aromatic containing carboxamides as potent SDH inhibitors. Eur. J. Med. Chem., 2021, 214, 113230.
[http://dx.doi.org/10.1016/j.ejmech.2021.113230] [PMID: 33581553]
[5]
Jo, J.; Lee, D.; Park, Y.H.; Choi, H.; Han, J.; Park, D.H.; Choi, Y.K.; Kwak, J.; Yang, M.K.; Yoo, J.W.; Moon, H.R.; Geum, D.; Kang, K.S.; Yun, H. Discovery and optimization of novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides as bifunctional antidiabetic agents stimu-lating both insulin secretion and glucose uptake. Eur. J. Med. Chem., 2021, 217, 113325.
[http://dx.doi.org/10.1016/j.ejmech.2021.113325] [PMID: 33765605]
[6]
Verma, R.; Verma, S.K.; Rakesh, K.P.; Girish, Y.R.; Ashrafizadeh, M.; Sharath Kumar, K.S.; Rangappa, K.S. Pyrazole-based analogs as potential antibacterial agents against methicillin-resistance staphylococcus aureus (MRSA) and its SAR elucidation. Eur. J. Med. Chem., 2021, 212, 113134.
[http://dx.doi.org/10.1016/j.ejmech.2020.113134] [PMID: 33395624]
[7]
Shanty, A.A.; Mohanan, P.V. Heterocyclic Schiff bases as non toxic antioxidants: Solvent effect, structure activity relationship and mechanism of action. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2018, 192, 181-187.
[http://dx.doi.org/10.1016/j.saa.2017.11.019] [PMID: 29136583]
[8]
Gebeyehu, G.M.; Feleke, D.G.; Molla, M.D.; Admasu, T.D. Effect of habitual consumption of Ethiopian Arabica coffee on the risk of cardiovascular diseases among non-diabetic healthy adults. Heliyon, 2020, 6(9), e04886.
[http://dx.doi.org/10.1016/j.heliyon.2020.e04886] [PMID: 32995603]
[9]
Channar, P.A.; Saeed, A.; Larik, F.A.; Batool, B.; Kalsoom, S.; Hasan, M.M.; Erben, M.F.; El-Seedi, H.R.; Ali, M.; Ashraf, Z. Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid. Bioorg. Chem., 2018, 79, 293-300.
[http://dx.doi.org/10.1016/j.bioorg.2018.04.026] [PMID: 29793142]
[10]
Orabi, E.A.; Orabi, M.A.A.; Mahross, M.H.; Abdel-Hakim, M. Computational investigation of the structure and antioxidant activity of some pyrazole and pyrazolone derivatives. J. Saudi Chem. Soc., 2018, 22(6), 705-714.
[http://dx.doi.org/10.1016/j.jscs.2017.12.003]
[11]
Shaitanova, E.N.; Balabon, O.A.; Rybakova, A.N.; Khlebnicova, T.S.; Lakhvich, F.A.; Gerus, I.I. Synthesis of functionalized fluoroalkyl pyrimidines and pyrazoles from fluoroalkyl enones. J. Fluor. Chem., 2021, 252, 109905.
[http://dx.doi.org/10.1016/j.jfluchem.2021.109905]
[12]
Annes, S.B.; Saritha, R.; Chandru, K.; Mandali, P.K.; Ramesh, S. Metal- and Solvent-Free Cascade Reaction for the Synthesis of Amino Pyrazole Thioether Derivatives. J. Org. Chem., 2021, 86(23), 16473-16484.
[http://dx.doi.org/10.1021/acs.joc.1c01846] [PMID: 34747592]
[13]
Konwar, M.; Hazarika, R.; Sarma, D. Synthetic advances in C(sp2)-H/N–H arylation of pyrazole derivatives through activation/substitution. Tetrahedron, 2021, 102, 132504.
[http://dx.doi.org/10.1016/j.tet.2021.132504]
[14]
Guo, H.; Zhang, Q.; Pan, W.; Yang, H.; Pei, K.; Zhai, J.; Li, T.; Wang, Z.; Wang, Y.; Yin, Y. One‐pot Synthesis of Substituted Pyrazoles from Propargyl Alcohols via Cyclocondensation of in situGenerated α‐Iodo Enones/Enals and Hydrazine Hydrate. Asian J. Org. Chem., 2021, 10(8), 2231-2237.
[http://dx.doi.org/10.1002/ajoc.202100318]
[15]
Zhao, J.; Qiu, J.; Gou, X.; Hua, C.; Chen, B. Iron(III) phthalocyanine chloride-catalyzed oxidation–aromatization of α,β-unsaturated ketones with hydrazine hydrate: Synthesis of 3,5-disubstituted 1H-pyrazoles. Chin. J. Catal., 2016, 37(4), 571-578.
[http://dx.doi.org/10.1016/S1872-2067(15)61043-9]
[16]
Mehta, K.; Khambete, M.; Abhyankar, A.; Omri, A. Anti-Tuberculosis Mur Inhibitors: Structural Insights and the Way Ahead for Development of Novel Agents. Pharmaceuticals (Basel), 2023, 16(3), 377.
[http://dx.doi.org/10.3390/ph16030377] [PMID: 36986477]
[17]
Tiwari, A.; Singh, A. Synthesis and evaluation of possible mechanism of anti nociceptive potential of novel 2-quinolone fused 3,5-pyrazolidinedione derivatives in experimental animal models. Comun. Conf. Vib. Constr. Mas., 2013, 24(1), 5-12.
[http://dx.doi.org/10.2478/auoc-2013-0001]
[18]
Gazvoda, M.; Virant, M.; Pevec, A.; Urankar, D.; Bolje, A.; Kočevar, M.; Košmrlj, J. A mesoionic bis(Py-tzNHC) palladium( II ) complex catalyses “green” Sonogashira reaction through an unprecedented mechanism. Chem. Commun. (Camb.), 2016, 52(8), 1571-1574.
[http://dx.doi.org/10.1039/C5CC08717A] [PMID: 26575368]
[19]
Tiwari, A.; Singh, A. Synthesis and antinociceptive activity of novel mannich base derivatives of some new fused 3,5-pyrazolidinedione. J. Adv. Pharm. Technol. Res., 2014, 5(1), 41-47.
[http://dx.doi.org/10.4103/2231-4040.126993] [PMID: 24696816]
[20]
Tiwari, A.; Tiwari, V.; Vankataramana, C.H.S.; Madhvan, V. Synthesis and Biological Activity of Pyrazolidine-3,5-Dione Substituted Benzimidazole Derivatives. Asian J. Chem., 2011, 23(3), 1179-1182.
[21]
Gupta, M.; Upmanyu, N.; Pramanik, S.; Chandekar, A. Synthesis and antimicrobial evaluation of 3,5-Pyrazolidine-dione substituted 4-quinolone derivatives. Int J. Drug Dev. & Res., 2011, 3(2), 233-239.
[22]
Gong, Y.; He, H.; Liu, H.; Zhang, C.; Zhao, W.; Shao, R. Phosphorylation of myofibrillogenesis regulator‐1 activates the MAPK signaling pathway and induces proliferation and migration in human breast cancer MCF7 cells. FEBS Lett., 2014, 588(17), 2903-2910.
[http://dx.doi.org/10.1016/j.febslet.2014.07.018] [PMID: 25066297]
[23]
Metwally, S.A.M.; Abdel Moneim, M.I.; Elossely, Y.A.; Awad, R.I.; Abou-Hadeed, K. Synthesis and crystal structure of some 3,5-pyrazolidinediones. Chem. Heterocycl. Compd., 2010, 46(4), 426-437.
[http://dx.doi.org/10.1007/s10593-010-0527-9]
[24]
Fritsch, G.; Zinner, G.; Mootz, D.; Scherf, M.; Wunderlich, H.N. Structure of a deaza dimer of 4-methyl-3H-1,2,4-triazole-3,5(4H)-dione. Arch. Pharm. (Weinheim), 1986, 319, 646-654.
[http://dx.doi.org/10.1002/ardp.19863190714]
[25]
Zivdar, M.; Salahvarzi, S.; Dadgar, Z. Derivatization of Curcumin and the Effect of Resultant Derivatives on BRC-9 Breast Cancer Cells. Iranian J Chem Chem Eng, 2022, 41(4), 1224-1231.

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