Phthalimide as a versatile pharmacophore scaffold: Unlocking its diverse biological activities

Fernandes, Guilherme; Lopes, Jair; Santos, Jean Leandro dos; Scarim, Cauê Benito

doi:10.1002/ddr.22094

Cited by 5 publications

(2 citation statements)

References 148 publications

(241 reference statements)

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“…Phthalimide is a versatile pharmacological scaffold with anticancer, anti-inflammatory, antiparasitic, and, importantly, antimicrobial activities ( Fernandes et al., 2023 ). Phthalimide and its derivatives also have various applications in the cosmetic and biomedicine industries ( Durairaju et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species

Shaik,

Lee,

Kim

et al. 2024

Front. Cell. Infect. Microbiol.

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Candida species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six N-substituted phthalimides against three Candida species. Of the derivatives, N-butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10–50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive Candida albicans and Candida parapsilosis. NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio parahaemolyticus, along with the polymicrobial biofilms of S. epidermidis and C. albicans. NBP markedly inhibited the hyphal formation and cell aggregation of C. albicans and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., ECE1, HWP1, and UME6, upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various Candida strains.

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Section: Discussionmentioning

confidence: 99%

Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species

Shaik,

Lee,

Kim

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Heterocyclic compounds have drawn the attention of scientists due to their ever-increasing need for therapeutic compounds. Phthalimide is a fused heterocyclic ring with a variety of therapeutic uses, including antibacterial [ 12 ], antiviral [ 13 ], anticancer [ 14 , 15 , 16 ], anticonvulsant [ 17 ], anti-EGFR [ 15 ], anti-inflammatory [ 18 ], inflammatory and neuropathic pain [ 19 ], antimalarial [ 20 ], schistosomiasis [ 21 ], and many more [ 22 , 23 ]. Some of phthalimide-based anticancer compounds include cantharidin, CC-11006, lenalidomide, pomalidomide, and thalidomide ( Figure 1 ) [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

An Efficient Synthesis of 1-(1,3-Dioxoisoindolin-2-yl)-3-aryl Urea Analogs as Anticancer and Antioxidant Agents: An Insight into Experimental and In Silico Studies

Afzal,

Ahsan

2023

Molecules

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The present investigation reports the efficient multistep synthesis of 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) in good yields. All the 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) were characterized by spectroscopic techniques. Five among the six compounds were tested against 56 cancer cell lines at 10 µM as per the standard protocol. 1-(4-Bromophenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7c) exhibited moderate but significant anticancer activity against EKVX, CAKI-1, UACC-62, MCF7, LOX IMVI, and ACHN with percentage growth inhibitions (PGIs) of 75.46, 78.52, 80.81, 83.48, 84.52, and 89.61, respectively. Compound 7c was found to exhibit better anticancer activity than thalidomide against non-small cell lung, CNS, melanoma, renal, prostate, and breast cancer cell lines. It was also found to exhibit superior anticancer activity against melanoma cancer compared to imatinib. Among the tested compounds, the 4-bromosubstitution (7c) on the phenyl ring demonstrated good anticancer activity. Docking scores ranging from −6.363 to −7.565 kcal/mol were observed in the docking studies against the molecular target EGFR. The ligand 7c displayed an efficient binding against the EGFR with a docking score of −7.558 kcal/mol and displayed an H-bond interaction with Lys745 and the carbonyl functional group. Compound 7c demonstrated a moderate inhibition of EGFR with an IC50 of 42.91 ± 0.80 nM, in comparison to erlotinib (IC50 = 26.85 ± 0.72 nM), the standard drug. The antioxidant potential was also calculated for the compounds (7a–f), which exhibited good to low activity. 1-(2-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7f) and 1-(4-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7d) demonstrated significant antioxidant activity with IC50 values of 15.99 ± 0.10 and 16.05 ± 0.15 µM, respectively. The 2- and 4-methoxysubstitutions on the N-phenyl ring showed good antioxidant activity among the series of compounds (7a–f). An in silico ADMET prediction studies showed the compounds’ adherence to Lipinski’s rule of five: they were free from toxicities, including mutagenicity, cytotoxicity, and immunotoxicity, but not for hepatotoxicity. The toxicity prediction demonstrated LD50 values between 1000 and 5000 mg/Kg, putting the compounds either in class IV or class V toxicity classes. Our findings might create opportunities for more advancements in cancer therapeutics.

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Direct synthesis of phthalimides via palladium-catalysed double carbonylation of o-dihaloarenes with nitroarenes

Liu,

An,

Yuan

et al. 2023

Chem. Commun.

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Phthalimide as a versatile pharmacophore scaffold: Unlocking its diverse biological activities

Cited by 5 publications

References 148 publications

Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species

Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species

An Efficient Synthesis of 1-(1,3-Dioxoisoindolin-2-yl)-3-aryl Urea Analogs as Anticancer and Antioxidant Agents: An Insight into Experimental and In Silico Studies

Direct synthesis of phthalimides via palladium-catalysed double carbonylation of o-dihaloarenes with nitroarenes

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