SYNTHESIS AND EVALUATION OF THE ANTICANCER ACTIVITY OF 2-AMINOISOINDOLE-THIZOLIDINONE HYBRIDS
DOI:
https://doi.org/10.11603/2312-0967.2023.4.14290Keywords:
organic synthesis, heterocycles, thiazolidinone, isoindole, anticancer activityAbstract
The aim of the work. Synthesis 2-aminoisoindole thizolidinone derivatives via [2+3]-cyclocondensation reaction using different equivalents of electrophilic synthon [C2]2+ and the anticancer activity screening in vitro of synthesized molecules.
Materials and Methods. Organic synthesis, NMR spectroscopy, pharmacological screening in vitro.
Results and Discussion. The [2+3]-cyclocondensation reaction of 1-(1,3-dioxoisoindolin-2-yl)thiourea with chloroacetic acid, N-arylmaleimides and β-aroylacrylic acids in glacial acetic acid allowed to obtain 5-substituted 2-aminoisoindole thizolidinone hybrids. Synthesis of indole-containing 2-aminoisoindole thizolidinones was performed by the one-pot three-component synthetic protocol of 1-(1,3-dioxoisoindolin-2-yl)thiourea, appropriative isatin, and monochloroacetic acid. The anticancer activity of synthesized compounds was studied at a concentration of 10-5 M on a panel of sixty cancer cells according to the standard protocols of the National Cancer Institute (NCI, Bethesda, MD, USA) Developmental Therapeutic Program (DTP).
Conclusions. An efficient method for synthesis new isoindole-thiazolidinones was studied. Indole-containing 2-aminoisoindole thizolidinone derivative demonstrated a moderate level of anticancer activity with an impact on melanoma, renal, and breast cancer cell lines.
References
Finiuk N, Kryshchyshyn-Dylevych A, Holota S, Klyuchivska O, Kozytskiy A, Karpenko O, Manko N, Ivasechko I, Stoika R, Lesyk R. Novel hybrid pyrrolidinedione-thiazolidinones as potential anticancer agents: Synthesis and biological evaluation. European Journal of Medicinal Chemistry. 2022;238: 114422. DOI: https://doi.org/10.1016/j.ejmech.2022.114422
Oubella A, El Mansouri AE, Fawzi M, Bimoussa A, Laamari Y, Auhmani A, Morjani H, Robert A, Riahi A, Itto MY. Thiazolidinone-linked1, 2, 3-triazoles with monoterpenic skeleton as new potential anticancer agents: Design, synthesis and molecular docking studies. Bioorganic Chemistry. 2021;115: 105184. DOI: https://doi.org/10.1016/j.bioorg.2021.105184
Salem MA, Abbas SY, El-Sharief MA, Alzahrani AY, Helal MH, Thabet HK. Synthesis and antimicrobial activity of 4-methylthiazole and 4-thiazolidinone derivatives derived from 5-(aryldiazo) salicylaldehyde thiosemicarbazones. Synthetic Communications. 2021;51(21): 3325-31. DOI: https://doi.org/10.1080/00397911.2021.1968909
Salian VV, Narayana B, Sarojini BK, Kodandoor SC, Lobo AG. Design, Synthesis, Docking and Computational Pharmacokinetic Profiling of New Pyrazolinyl Thiazolinone Biheterocycles as Potent Antimicrobial Agents. Letters in Drug Design & Discovery. 2020;17(11):1342-54. DOI: https://doi.org/10.2174/1570180817999200623115049
Kryshchyshyn A, Kaminskyy D, Karpenko O, Gzella A, Grellier P, Lesyk R. Thiazolidinone/thiazole based hybrids–New class of antitrypanosomal agents. European journal of medicinal chemistry. 2019;174: 292-308. DOI: https://doi.org/10.1016/j.ejmech.2019.04.052
Ghous F, Shukla S, Singh R, Parveen S, Banerjee M, Bishnoi A. Synthesis, crystal structure, computational investigation, molecular docking analysis and anti-lung cancer activity of novel (Z)-3-amino-2-(cyclohexylidenehydrazono) thiazolidin-4-one. Journal of Molecular Structure. 2023;1285: 135462. DOI: https://doi.org/10.1016/j.molstruc.2023.135462
Khan S, Iqbal S, Rahim F, Shah M, Hussain R, Alrbyawi H, Rehman W, Dera AA, Rasheed L, Somaily HH, Pashameah RA. New biologically hybrid pharmacophore thiazolidinone-based indole derivatives: synthesis, in vitro alpha-amylase and alpha-glucosidase along with molecular docking investigations. Molecules. 2022;27(19): 6564. DOI: https://doi.org/10.3390/molecules27196564
Mushtaque M, Rizvi MA. Molecular hybrids based on Pyrazole and 4-Thiazolidinone cores: Synthesis, characterization, and anticancer studies. Journal of Molecular Structure. 2023;1294: 136470. DOI: https://doi.org/10.1016/j.molstruc.2023.136470
Sigalapalli DK, Pooladanda V, Singh P, Kadagathur M, Guggilapu SD, Uppu JL, Tangellamudi ND, Gangireddy PK, Godugu C, Bathini NB. Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study. Bioorganic Chemistry. 2019;92: 103188. DOI: https://doi.org/10.1016/j.bioorg.2019.103188
Donarska B, Świtalska M, Płaziński W, Wietrzyk J, Łączkowski KZ. Effect of the dichloro-substitution on antiproliferative activity of phthalimide-thiazole derivatives. Rational design, synthesis, elastase, caspase 3/7, and EGFR tyrosine kinase activity and molecular modeling study. Bioorganic Chemistry. 2021;110: 104819. DOI: https://doi.org/10.1016/j.bioorg.2021.104819
Ihmaid SK, Alraqa SY, Aouad MR, Aljuhani A, Elbadawy HM, Salama SA, Rezki N, Ahmed HE. Design of molecular hybrids of phthalimide-triazole agents with potent selective MCF-7/HepG2 cytotoxicity: Synthesis, EGFR inhibitory effect, and metabolic stability. Bioorganic Chemistry. 2021;111: 104835. DOI: https://doi.org/10.1016/j.bioorg.2021.104835
Shehta W, Agili F, Farag B, Youssif S, Almehmadi SJ, Elfeky SM, El-Kalyoubi S. Synthesis and in vitro study of pyrimidine–phthalimide hybrids as VEGFR2 inhibitors with antiproliferative activity. Future Medicinal Chemistry. 2023;15(8): 661-77. DOI: https://doi.org/10.4155/fmc-2023-0025
Philoppes JN, Lamie PF. Design and synthesis of new benzoxazole/benzothiazole-phthalimide hybrids as antitumor-apoptotic agents. Bioorganic chemistry. 2019;89: 102978. DOI: https://doi.org/10.1016/j.bioorg.2019.102978
de Oliveira Cardoso MV, Moreira DR, Oliveira Filho GB, Cavalcanti SM, Coelho LC, Espíndola JW, Gonzalez LR, Rabello MM, Hernandes MZ, Ferreira PM, Pessoa C. Design, synthesis and structure–activity relationship of phthalimides endowed with dual antiproliferative and immunomodulatory activities. European Journal of Medicinal Chemistry. 2015;96: 491-503. DOI: https://doi.org/10.1016/j.ejmech.2015.04.041
Prajapat P, Talesara GL. New benzothiazole-thiazolidinone hybrids containing phthalimidoxy and ethoxyphthalimide: Design, synthesis and pharmacological assay. Organic & Medicinal Chemistry International Journal. 2018;5(5): 148-154. DOI: https://doi.org/10.19080/OMCIJ.2018.05.555673
Santos FA, Almeida ML, Silva VA, Viana DC, Pereira MC, Lucena AS, Pitta MG, Galdino-Pitta MR, de Melo Rêgo MJ, da Rocha Pitta I. Synthesis and biological activities of new phthalimide and thiazolidine derivatives. Medicinal Chemistry Research. 2022;31(1): 108-119. DOI: https://doi.org/10.1007/s00044-021-02821-7
Oliveira AR, Dos Santos FA, de Lima Ferreira LP, da Rocha Pitta MG, de Oliveira Silva MV, de Oliveira Cardoso MV, Pinto AF, Marchand P, de Melo Rêgo MJ, Leite AC. Synthesis, anticancer activity and mechanism of action of new phthalimido-1, 3-thiazole derivatives. Chemico-Biological Interactions. 2021;347: 109597. DOI: https://doi.org/10.1016/j.cbi.2021.109597
Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A, Gray-Goodrich M. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. JNCI: Journal of the National Cancer Institute. 1991;83(11): 757-66. DOI: https://doi.org/10.1093/jnci/83.11.757
Boyd MR, Paull KD. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug development research. 1995;34(2): 91-109. DOI: https://doi.org/10.1002/ddr.430340203
Boyd MR. The NCI in vitro anticancer drug discovery screen. In: Anticancer Drug Development Guide. Totowa, NJ: Humana Press; 1997. DOI: https://doi.org/10.1007/978-1-4615-8152-9_2
Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nature Reviews Cancer. 2006;6(10): 813-23. DOI: https://doi.org/10.1038/nrc1951
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Pharmaceutical Review / Farmacevtičnij časopis
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors who publish their materials in this journal agree with the following terms:
- Authors reserve the right to authorship of their work and assign to the journal the right to first publish this work under the terms of the Creative Commons Attribution License, which allows other persons to freely distribute the published work with a mandatory reference to the authors of original work and the first publication of work in this journal
. - Authors have the right to make independent extra-exclusive work agreements in the form they are published by this journal (for example, posting work in an electronic repository of an institution or publishing as part of a monograph), provided that the link to the first publication of the work in this journal is maintained.
Journal policy allows and encourages publication of manuscripts on the Internet (for example, in institutions repositories or on personal websites), both before the publication of this manuscript and during its editorial review, as it contributes to productive scientific discussion and positively affects the efficiency and dynamics of the citation of the published work (see The Effect of Open Access).
