Synthesis and anticancer activity of Pt(II) complexes of spiro-5-substituted 2,4-dithiohydantoins

Ahmedova, Anife; Pavlović, Gordána; Marinov, Marin; Marinova, Petja; Momekov, Georgi; Paradowska, Katarzyna; Yordanova, Stanislava; Stoyanov, Stanimir; Vassilev, Nikolay G.; Stoyanov, Neyko

doi:10.1016/j.ica.2021.120605

Cited by 6 publications

(2 citation statements)

References 47 publications

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“…The discovery of biologically active compounds embedded in spirooxinole and hydantoin scaffolds prompted us to investigate further modifications within this class of compounds. Similarly, hydantoin derivatives (imidazolidine-2,4-diones) [28,29] emerged as privileged scaffolds in medicinal chemistry due to their various biological and therapeutic applications such as anticancer [30][31][32], anti-inflammatory [33][34][35], antidiabetic [36], anticonvulsant [37,38] and antimicrobial agents [39]. With such broad bioactivities, many hydantoin derivatives featured in several clinically used drugs such as phenytoin (anti-epileptic agent) [40], nilutamide (nonsteroidal androgen antagonists) [41] and nitrofurantoin (antibiotic for the treatment of infections caused by multi-drug resistant pathogens) (Figure 1) [42].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities

Toumi,

Abdella,

Boudriga

et al. 2023

Molecules

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In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC50 = 1.09 mg/mL and IC50 = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC50 = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities

Toumi,

Abdella,

Boudriga

et al. 2023

Molecules

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“…Spirocyclic skeletons are important synthetic targets due to their diversified biological activities and have been used as core components of various functional materials and ligands . With the rapid development of C–H bond functionalization, transition-metal-catalyzed annulation reactions have proven to be a powerful tool for obtaining various challenging but synthetically valuable spirocyclic molecules .…”

mentioning

confidence: 99%

Ruthenium(II)-Catalyzed Regioselective [3 + 2] Spiroannulation of 2H-Imidazoles with 2-Alkynoates

et al. 2020

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The CN double bond of 2H-imidazole has been employed as a C-electrophile for the ruthenium(II)-catalyzed [3 + 2] spiroannulation reaction of 4-phenyl-2H-imidazoles and 2alkynoates to synthesize spiroimidazole-4,1′-indenes. This strategy features high regioselectivity, broad functional group tolerance, and use of ruthenium as a catalyst, providing a new method to synthesize spirocycles with potential applications in pharmaceuticals.

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Progress on the coordination chemistry and application of hydantoins and its derivatives as anticorrosive materials for steel: A review

Akpan

Dagdag

Ebenso

2023

Coordination Chemistry Reviews

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Synthesis and anticancer activity of Pt(II) complexes of spiro-5-substituted 2,4-dithiohydantoins

Cited by 6 publications

References 47 publications

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities

Ruthenium(II)-Catalyzed Regioselective [3 + 2] Spiroannulation of 2H-Imidazoles with 2-Alkynoates

Progress on the coordination chemistry and application of hydantoins and its derivatives as anticorrosive materials for steel: A review

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