Synthesis of novel 5-substituted 2-pyrazolylthiazol-4-ones as potential bioligically active compounds

Authors

  • I. M. Yushyn Danylo Halytsky Lviv National Medical University, Ukraine,
  • A. V. Lozynskyi Danylo Halytsky Lviv National Medical University, Ukraine,
  • O.-M. V. Fedusevych Danylo Halytsky Lviv National Medical University, Ukraine,
  • O. Yа. Vovchuk Danylo Halytsky Lviv National Medical University, Ukraine,
  • R. B. Lesyk Danylo Halytsky Lviv National Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2020.2.207117

Keywords:

hybrid-pharmacophore approach, thiazolo-pyrazoline conjugates, [2 3]-cyclocondensation reaction, NMR spectroscopy

Abstract

One of the effective strategies in potential “drug-like” molecules design is using a molecular hybridization approach based on the combination of several pharmacological scaffolds in one molecule. The main argument for using this approach is a polypharmacological theory based on the interaction of mentioned hybrid molecules with multiple bio-targets based on selectivity and the resulting reduction of toxicity.

The aim of the work is to synthesize a number of new 5-substituted 2-pyrazolylthiazol-4-ones as potentional biologically active compounds.

Materials and methods. Organic synthesis, 1H NMR spectroscopy.

Results. The synthesis of new 5-ene-2-pyrazolylthiazol-4-ones was carried out via a three-component [2+3]-cyclocondensation reaction of 3-methyl-5-aryl-4,5-dihydropyrazole-1-carbothiamides with chloroacetic acid and the corresponding carbonyl compounds in acetic acid medium. The structure of the synthesized compounds was confirmed by elemental analysis and 1H NMR spectroscopy.

Conclusions. As a result of chemical transformations, a library of new thiazole-pyrazoline conjugates was synthesized based on a hybrid-pharmacophore approach to further anticancer activity evaluation within the DTP NCI protocol.

 

References

Lesyk, R. B., & Zimenkovsky, B. S. (2004). 4-thiazolidones: Centena­rian history, current status and perspectives for modern organic and medicinal chemistry. Current Organic Chemistry, 8(16), 1547-1577. https://doi.org/10.2174/1385272043369773

Havrylyuk, D., Zimenkovsky, B., Vasylenko, O., Gzella, A., & Lesyk, R. (2012). Synthesis of New 4-Thiazolidinone-, Pyrazoline-, and Isatin-Based Conjugates with Promising Antitumor Activity. Journal of Medicinal Chemistry, 55(20), 8630-8641. https://doi.org/10.1021/jm300789g

Saeed, A., Mahesar, P. A., Channar, P. A., Larik, F. A., Abbas, Q., Hassan, M., Raza, H., & Seo, S. Y. (2017). Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyra­zolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking. Chemistry & Biodiversity, 14(8), Article e1700035. https://doi.org/10.1002/cbdv.201700035

Kumar, P., Duhan, M., Kadyan, K., Sindhu, J., Kumar, S., & Sharma, H. (2017). Synthesis of novel inhibitors of α-amylase based on the thiazolidine-4-one skeleton containing a pyrazole moiety and their configurational studies. MedChemComm, 8(7), 1468-1476. https://doi.org/10.1039/c7md00080d

Saczewski, J., Paluchowska, A., Klenc, J., Raux, E., Barnes, S., Sullivan, S., … Strekowskia, L. (2009). Synthesis of 4-substituted 2-(4-methylpiperazino)pyrimidines and quinazoline analogs as serotonin 5-HT2A receptor ligands. Journal of Heterocyclic Chemistry, 46(6), 1259-1265. https://doi.org/10.1002/jhet.236

Abu-Hashem, A. A., & Aly, A. S. (2012). Synthesis of new pyrazole, triazole, and thiazolidine-pyrimido [4, 5-b] quinoline derivatives with potential antitumor activity. Archives of pharmacal research, 35(3), 437-445. https://doi.org/10.1007/s12272-012-0306-5

Abeed, A., El-Emary, T. I., & Youssef, M. (2019). A Facile Synthesis and Reactions of Some Novel Pyrazole-based Heterocycles. Current organic synthesis, 16(3), 405-412. https://doi.org/10.2174/1570179416666181210160908

Gondru, R., Sirisha, K., Raj, S., Gunda, S. K., Kumar, C. G., Pasupuleti, M., & Bavantula, R. (2018). Design, Synthesis, In Vitro Evaluation and Docking Studies of Pyrazole-Thiazole Hybrids as Antimicrobial and Antibiofilm Agents. Chemistryselect, 3(28), 8270-8276. https://doi.org/10.1002/slct.201801391

Abdellatif, K. R. A., Abdelgawad, M. A., Elshemy, H. A. H., Kahk, N. M., & El Amir, D. M. (2017). Design, Synthesis, Antioxidant and Anticancer Activity of New Coumarin Derivatives Linked with Thiazole, Isoxa­zole or Pyrazole Moiety. Letters in Drug Design & Discovery, 14(7), 773-781. https://doi.org/10.2174/1570180813666161026153743

Kryshchyshyn, A., Kaminskyy, D., Karpenko, O., Gzella, A., Grellier, P., & Lesyk, R. (2019). Thiazolidinone/thiazole based hybrids – New class of antitrypanosomal agents. European Journal of Medicinal Chemistry, 174, 292-308. https://doi.org/10.1016/j.ejmech.2019.04.052

Alvarez, G., Martinez, J., Varela, J., Birriel, E., Cruces, E., … Cerecetto, H. (2015). Development of bis-thiazoles as inhibitors of triosephosphate isomerase from Trypanosoma cruzi. Identification of new non-mutagenic agents that are active in vivo. European Journal of Medicinal Chemistry, 100, 246-256. https://doi.org/10.1016/j.ejmech.2015.06.018

Holota, S., Derkach, H., Demchuk, I. L., Vynnytska, R. B., Antoniv, O. I., Furdychko, L. O., Slyvka, N., Nektegayev, I., Lesyk, R. B. (2019). Synthesis and In vivo evaluation of pyrazoline-thiazolidin-4-one hybrid Les-5581 as a potential non-steroidal anti-inflammatory agent. Biopolymers and Cell, 35(6), 437-447. https://doi.org/10.7124/bc.000A17

Kamble, R. D., Meshram, R. J., Hese, S. V., More, R. A., Kamble, S. S., Gacche, R. N., & Dawane, B. S. (2016). Synthesis and in silico investigation of thiazoles bearing pyrazoles derivatives as anti-inflammatory agents. Computational Biology and Chemistry, 61, 86-96. https://doi.org/10.1016/j.compbiolchem.2016.01.007

Abdellatif, K., Fadaly, W., Kamel, G., Elshaier, Y., & El-Magd, M. (2019). Design, synthesis, modeling studies and biological evaluation of thiazolidine derivatives containing pyrazole core as potential anti-diabetic PPAR-γ agonists and anti-inflammatory COX-2 selective inhibitors. Bioorganic Chemistry, 82, 86-99. https://doi.org/10.1016/j.bioorg.2018.09.034

Havrylyuk, D., Zimenkovsky, B., Vasylenko, O., Zaprutko, L., Gzella, A., & Lesyk, R. (2009). ChemInform Abstract: Synthesis of Novel Thiazolone-Based Compounds Containing Pyrazoline Moiety and Evaluation of Their Anticancer Activity. European Journal of Medicinal Chemistry, 44(4), 1396-1404. https://doi.org/10.1002/chin.200931120

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How to Cite

1.
Yushyn IM, Lozynskyi AV, Fedusevych O-MV, Vovchuk OY, Lesyk RB. Synthesis of novel 5-substituted 2-pyrazolylthiazol-4-ones as potential bioligically active compounds. CIPM [Internet]. 2020Jul.3 [cited 2023Dec.8];13(2). Available from: http://pharmed.zsmu.edu.ua/article/view/207117

Issue

Vol. 13 No. 2 (2020)

Section

Original research

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