A Novel Naphthotriazolyl-4-oxoquinoline Derivative that Selectively Controls Breast Cancer Cells Survival Through the Induction of Apoptosis

Branco, Jessica Ristow; Oliveira, Vanessa G.; Esteves, Amanda M.; Chipoline, Ingrid C.; Lima, Miriam F.O.; Boechat, Fernanda da Costa Santos; Silva, Fernando C. da; Ferreira, Vı́tor F.; Sola‐Penna, Mauro; Souza, Maria Cecília B. V. de; Zancan, Patrícia

doi:10.2174/1568026618666180821142458

Cited by 9 publications

(4 citation statements)

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“…without altering mitochondrial potential, increased reactive oxygen species production, and reduced cell glucose consumption and lactate production, which are critical in the central metabolic pathway for cancer cells [23]. Biological properties have been identified by our research group, confirming the success of the conjugation strategy between these two frameworks of medicinal chemistry interest in identifying new bioactive prototypes [24,25].…”

Section: Introductionsupporting

confidence: 70%

“…Among the conjugates obtained, compound 10 ( Figure 3 ) demonstrated activity against three different breast cancer cell lines: MCF-7, MDA-MB-231, and 4T1. This compound exhibited high selectivity, showing no significant cytotoxicity against the non-cancerous cell line MCF10A, unlike doxorubicin [ 23 ]. Moreover, in the MCF-7 cell line, compound 10 selectively promoted apoptosis, decreased intracellular ATP levels without altering mitochondrial potential, increased reactive oxygen species production, and reduced cell glucose consumption and lactate production, which are critical in the central metabolic pathway for cancer cells [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…This compound exhibited high selectivity, showing no significant cytotoxicity against the non-cancerous cell line MCF10A, unlike doxorubicin [ 23 ]. Moreover, in the MCF-7 cell line, compound 10 selectively promoted apoptosis, decreased intracellular ATP levels without altering mitochondrial potential, increased reactive oxygen species production, and reduced cell glucose consumption and lactate production, which are critical in the central metabolic pathway for cancer cells [ 23 ]. Biological properties have been identified by our research group, confirming the success of the conjugation strategy between these two frameworks of medicinal chemistry interest in identifying new bioactive prototypes [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Some data from our group have demonstrated that hybrid compounds derived from quinones also have anticancer activity, and it was seen that these compounds interfere in cell metabolism of breast cancer cells by decreasing glucose consumption, lactate production, and ATP intracellular levels. Moreover, these compounds increased ROS production, as a consequence of mitochondrial membrane depolarization (Bortolot et al, 2019; Branco et al, 2018).…”

Section: Isoquinolines Chemotherapymentioning

confidence: 99%

Isoquinolines alkaloids and cancer metabolism: Pathways and targets to novel chemotherapy

Mello

Zancan

2022

Chem Biol Drug Des

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Cancer is one of the main causes of death in the world. This is a complex disease where the development of resistance to chemotherapy is frequent driving the search for new anticancer compounds. In this sense, isoquinolines have gained attention in the past few years. This review aims to highlight the new advances related to the use of isoquinolines compounds against cancer cells, and we point out targets for their anti-tumor action. Isoquinolines are compounds found in plants that are important for their protection. In cancer, many representatives of this class of compounds have demonstrated their efficacy against cancer by acting on cancer metabolism, such as triggering cell death, reducing pro-survival protein expression, inducing ROS production, inhibiting pro-survival cell signaling pathways, among other effects. The mechanisms triggered by isoquinolines in cancer cells represent robust anticancer strategies, which support that this class of compounds are strong candidates for cancer treatment.

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Bioactive 1,2,3‐Triazoles: An Account on their Synthesis, Structural Diversity and Biological Applications

Forezi

Lima

Amaral

et al. 2021

The Chemical Record

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The triazole heterocycle is a privileged scaffold in medicinal chemistry, since its structure is present in a large number of biologically active molecules, including several drugs currently in the market. Due to their vast applications, a wide variety of methods are described for their preparation, such as the 1,3‐dipolar cycloaddition and processes involving diazo compounds and diazo transfer reactions. Considering the significant number of contributions from our research group to this chemistry in recent decades, in this account we discuss both the development of new methods for the synthesis of 1,2,3‐triazoles and the preparation of new triazole‐functionalized biologically active molecules using classical approaches.

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A Novel Naphthotriazolyl-4-oxoquinoline Derivative that Selectively Controls Breast Cancer Cells Survival Through the Induction of Apoptosis

Cited by 9 publications

References 0 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

Isoquinolines alkaloids and cancer metabolism: Pathways and targets to novel chemotherapy

Bioactive 1,2,3‐Triazoles: An Account on their Synthesis, Structural Diversity and Biological Applications

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