Therapeutic Potential of Phthalimide Derivatives: A Review

Júnior, José Guedes da Silva; Holanda, Vanderlan Nogueira; RodriguesGambôa, Daywison Silva; Monte, Talyta Valéria Siqueira do; Júnior, JoséAdelson Alves do Nascimento; Araújo, Victor Felipe da Silva; Callôu, Maria AuxiliadoraMacedo; Assis, Shalom Pôrto de Oliveira; Lima, Vera L. M.

doi:10.34297/ajbsr.2019.03.000699

Cited by 10 publications

(2 citation statements)

References 37 publications

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“…These compounds are hydrophobic, endowing the molecule with the ability to traverse biological membranes in vivo [ 136 ]. In addition, these molecules and some of their derivatives are endowed with antibacterial, antifungal, analgesic, antitumor, anxiolytic, hypolipemic, and analgesic activities and have low in vivo toxicity [ 137 ].…”

Section: Ferruginol Analogs As Potential Host-targeted Antiviralmentioning

confidence: 99%

Host Cell Targets for Unconventional Antivirals against RNA Viruses

Roa-Linares

Escudero-Flórez

Vicente‐Manzanares

et al. 2023

Viruses

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The recent COVID-19 crisis has highlighted the importance of RNA-based viruses. The most prominent members of this group are SARS-CoV-2 (coronavirus), HIV (human immunodeficiency virus), EBOV (Ebola virus), DENV (dengue virus), HCV (hepatitis C virus), ZIKV (Zika virus), CHIKV (chikungunya virus), and influenza A virus. With the exception of retroviruses which produce reverse transcriptase, the majority of RNA viruses encode RNA-dependent RNA polymerases which do not include molecular proofreading tools, underlying the high mutation capacity of these viruses as they multiply in the host cells. Together with their ability to manipulate the immune system of the host in different ways, their high mutation frequency poses a challenge to develop effective and durable vaccination and/or treatments. Consequently, the use of antiviral targeting agents, while an important part of the therapeutic strategy against infection, may lead to the selection of drug-resistant variants. The crucial role of the host cell replicative and processing machinery is essential for the replicative cycle of the viruses and has driven attention to the potential use of drugs directed to the host machinery as therapeutic alternatives to treat viral infections. In this review, we discuss small molecules with antiviral effects that target cellular factors in different steps of the infectious cycle of many RNA viruses. We emphasize the repurposing of FDA-approved drugs with broad-spectrum antiviral activity. Finally, we postulate that the ferruginol analog (18-(phthalimide-2-yl) ferruginol) is a potential host-targeted antiviral.

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Section: Ferruginol Analogs As Potential Host-targeted Antiviralmentioning

confidence: 99%

Host Cell Targets for Unconventional Antivirals against RNA Viruses

Roa-Linares

Escudero-Flórez

Vicente‐Manzanares

et al. 2023

Viruses

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“…The phthalimide (Pht) scaffold has attracted great interest as the basis for the synthesis of various alkaloids and other biologically important pharmacophores [25][26][27][28][29]. Phts are lipophilic and neutral molecules that can easily cross biological membranes, and possess anti-microbial [30] and anti-inflammatory [31] activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Bioactivity of Phthalimide Analogs as Potential Drugs to Treat Schistosomiasis, a Neglected Disease of Poverty

et al. 2020

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The neglected tropical disease, schistosomiasis, is caused by trematode blood flukes of the Schistosoma genus and infects approximately 200 million people worldwide. With just one partially effective drug available for disease treatment, new drugs are urgently needed. Herein, a series of 47 phthalimide (Pht) analogues possessing high-value bioactive scaffolds (i.e., benzimidazole and 1,2,3,-triazoles) was synthesized by click-chemistry. Compounds were evaluated for anti-schistosomal activity in culture against somules (post-infective larvae) and adults of Schistosoma mansoni, their predicted ADME (absorption, distribution, metabolism, and excretion) properties, and toxicity vs. HepG2 cells. The majority showed favorable parameters for surface area, lipophilicity, bioavailability and Lipinski score. Thirteen compounds were active at 10 µM against both somules and adults (6d, 6f, 6i-6l, 6n-6p, 6s, 6r', 6t' and 6w). Against somules, the majority caused degeneracy and/or death after 72 h; whereas against adult parasites, five compounds (6l, 6d, 6f, 6r' and 6s) elicited degeneracy, tegumental (surface) damage and/or death. Strongest potency against both developmental stages was recorded for compounds possessing n-butyl or isobutyl as a linker, and a pentafluorophenyl group on triazole. Apart from five compounds for which anti-parasite activity tracked with toxicity to HepG2 cells, there was apparently no toxicity to HepG2 cells (EC 50 values ≥50 µM). The data overall suggest that phthaloyl-triazole compounds are favorable synthons for additional studies as anti-schistosomals.

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

Fernandes

Lopes

Santos

et al. 2023

Drug Development Research

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Phthalimide, a pharmacophore exhibiting diverse biological activities, holds a prominent position in medicinal chemistry. In recent decades, numerous derivatives of phthalimide have been synthesized and extensively studied for their therapeutic potential across a wide range of health conditions. This comprehensive review highlights the latest developments in medicinal chemistry, specifically focusing on phthalimide‐based compounds that have emerged within the last decade. These compounds showcase promising biological activities, including anti‐inflammatory, anti‐Alzheimer, antiepileptic, antischizophrenia, antiplatelet, anticancer, antibacterial, antifungal, antimycobacterial, antiparasitic, anthelmintic, antiviral, and antidiabetic properties. The physicochemical profiles of the phthalimide derivatives were carefully analyzed using the online platform pkCSM, revealing the remarkable versatility of this scaffold. Therefore, this review emphasizes the potential of phthalimide as a valuable scaffold for the development of novel therapeutic agents, providing avenues for the exploration and design of new compounds.

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Therapeutic Potential of Phthalimide Derivatives: A Review

Abstract: This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.000699

Cited by 10 publications

References 37 publications

Host Cell Targets for Unconventional Antivirals against RNA Viruses

Host Cell Targets for Unconventional Antivirals against RNA Viruses

Synthesis and Bioactivity of Phthalimide Analogs as Potential Drugs to Treat Schistosomiasis, a Neglected Disease of Poverty

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

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