Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs

Andrade, Silmara Nunes; Evangelista, Fernanda Cristina Gontijo; Seckler, Diego; Marques, Deisielly Ribeiro; Freitas, Túlio Resende; Nunes, Renata Rachide; Oliveira, Jorge de; Ribeiro, Rosy Iara Maciel de Azambuja; Santos, Hélio Batista dos; Thomé, Ralph Gruppi; Taranto, Alex Gutterres; Santos, Fábio V.; Viana, Gustavo Henrique Ribeiro; Freitas, Rossimiriam Pereira de; Humberto, Jorge Luiz; Sabino, Adriano de Paula; Hilário, Flaviane Francisco; Varotti, Fernando P.

doi:10.1007/s00044-018-2244-3

Cited by 4 publications

(3 citation statements)

References 54 publications

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“…Among them, compound 29 was found to be the most potent anti-breast cancer agent, with an IC 50 value of 19.48 µM against the MDA-MDB-231 breast cancer cells. The structure–activity relationship suggested that the substitution of a longer carbon chain linked to the phenyl ring via an amide linkage was beneficial for the activity of the compound, while decreases in the length of the chain led to decreased activity [ 100 ]. Ganeshapillai et al designed and synthesized C-3- and C-4-substituted bicyclic coumarin sulfamate (compound 30 ), which was effective against MCF-7 cells, with an IC 50 value of 0.68 µM.…”

Section: Synthetic Coumarin-inspired Derivatives With Anti-breast Can...mentioning

confidence: 99%

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure–Activity Relationships

Singh,

Kaur

et al. 2024

Biomedicines

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Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure–activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.

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Section: Synthetic Coumarin-inspired Derivatives With Anti-breast Can...mentioning

confidence: 99%

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure–Activity Relationships

Singh,

Kaur

et al. 2024

Biomedicines

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“…Further studies conducted with chemo-resistant cancer cells (i.e., A2780CisR and Cal27CisR) revealed that some of these potent derivatives actually increase the potency of cisplatin in a synergistic manner. Further, Andrade et al (2018) explored the moiety of natural HDACi santacruzamate A to produce seven synthetic compounds that were tested against a panel of human cancer lines that included breast cancer cells MCF-7 and MDA-MB-231 as well as ovarian cancer cell TOV-21G to have moderate micromolar potencies. Even though in vitro potencies of these compounds against HDACs were not reported, further investigation revealed that the most potent compound of this series may indeed enhance DNA damage and may promote apoptotic cell death through intrinsic pathway.…”

Section: Development Hdaci Against Ovarian Carcinomamentioning

confidence: 99%

Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer

Pramanik

Halder²,

Mukherjee³

et al. 2022

Front. Chem.

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Histone deacetylases (HDACs) are enzymes that play a role in chromatin remodeling and epigenetics. They belong to a specific category of enzymes that eliminate the acetyl part of the histones’ -N-acetyl lysine, causing the histones to be wrapped compactly around DNA. Numerous biological processes rely on HDACs, including cell proliferation and differentiation, angiogenesis, metastasis, gene regulation, and transcription. Epigenetic changes, specifically increased expression and activity of HDACs, are commonly detected in cancer. As a result, HDACi could be used to develop anticancer drugs. Although preclinical outcomes with HDACs as monotherapy have been promising clinical trials have had mixed results and limited success. In both preclinical and clinical trials, however, combination therapy with different anticancer medicines has proved to have synergistic effects. Furthermore, these combinations improved efficacy, decreased tumor resistance to therapy, and decreased toxicity. In the present review, the detailed modes of action, classification of HDACs, and their correlation with different cancers like prostate, breast, and ovarian cancer were discussed. Further, the different cell signaling pathways and the structure-activity relationship and pharmaco-toxicological properties of the HDACi, and their synergistic effects with other anticancer drugs observed in recent preclinical and clinical studies used in combination therapy were discussed for prostate, breast, and ovarian cancer treatment.

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“…The initial publication about its discovery also reported picomolar-level selective inhibitory activity against HDAC2 (IC50 = 119 pM), with a relatively weak inhibition of HDAC4 and HDAC6 [1]. Although these data were not entirely corroborated by later publications from the same group [3] and others [4][5][6], the interest drawn by this natural product has led to the preparation of many analogues, some with promising bioactivity [4][5][6][7][8]. Considering the current interest in this topic and the ongoing investigations of the structureactivity relationships, we saw an opportunity to contribute to the availability of structurally diverse Santacruzamate A analogues with our method for β-keto amide synthesis [9].…”

Section: Introductionmentioning

confidence: 98%

Oxygenated Analogues of Santacruzamate A

Angelov

Manolov

Yanev

et al. 2021

Molbank

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Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs

Cited by 4 publications

References 54 publications

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure–Activity Relationships

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure–Activity Relationships

Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer

Oxygenated Analogues of Santacruzamate A

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