Aminoquinolones and Their Benzoquinone Dimer Hybrids as Modulators of Prion Protein Conversion

Costa, Amanda Rodrigues Pinto; Muxfeldt, Marcelly; Boechat, Fernanda da Costa Santos; Souza, Maria Cecília B. V. de; Silva, Jerson L.; Moraes, Marcela Cristina de; Rangel, Luciana P.; Vieira, Tuane C. R. G.; Batalha, Pedro N.

doi:10.3390/molecules27227935

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…The two-dimensional experiments were conducted using standard Varian Associates automated programs used for data acquisition and processing. Compounds 13 , 14a – c , 15a – c , and 16a – c were synthesized as described in previous works [ 25 , 42 , 43 ].…”

Section: Methodsmentioning

confidence: 99%

Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects

da Gama Oliveira,

Muxfeldt,

Muniz da Paz

et al. 2024

IJMS

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Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC50 values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy.

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Section: Methodsmentioning

confidence: 99%

Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects

da Gama Oliveira,

Muxfeldt,

Muniz da Paz

et al. 2024

IJMS

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In vitro and in silico DNA interaction studies of a series of 3-carboxamide-4-quinolone derivatives prepared from an one-pot stepwise synthesis (OPSS) method

do Vale,

de Oliveira Andrade,

Cunha

et al. 2025

Journal of Molecular Structure

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Perspectives on CRISPR Genome Editing to Prevent Prion Diseases in High-Risk Individuals

Medd,

Cao

2024

Biomedicines

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Prion diseases are neurodegenerative disorders caused by misfolded prion proteins. Although rare, the said diseases are always fatal; they commonly cause death within months of developing clinical symptoms, and their diagnosis is exceptionally difficult pre-mortem. There are no known cures or treatments other than symptomatic care. Given the aggressiveness of prion diseases on onset, therapies after disease onset could be challenging. Prevention to reduce the incidence or to delay the disease onset has been suggested to be a more feasible approach. In this perspective article, we summarize our current understandings of the origin, risk factors, and clinical manifestations of prion diseases. We propose a PCR testing of the blood to identify PRNP gene polymorphisms at codons 129 and 127 in individuals with familial PRNP mutations to assess the risk. We further present the CRISPR/Cas9 gene editing strategy as a perspective preventative approach for these high-risk individuals to induce a polymorphic change at codon 127 of the PRNP gene, granting immunity to prion diseases in selected high-risk individuals, in particular, in individuals with familial PRNP mutations.

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Aminoquinolones and Their Benzoquinone Dimer Hybrids as Modulators of Prion Protein Conversion

Cited by 3 publications

References 39 publications

Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects

Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects

In vitro and in silico DNA interaction studies of a series of 3-carboxamide-4-quinolone derivatives prepared from an one-pot stepwise synthesis (OPSS) method

Perspectives on CRISPR Genome Editing to Prevent Prion Diseases in High-Risk Individuals

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