Synthesis and antitumor activity of some cholesterol-based selenocyanate compounds

Huang, Yanmin; Cheng, Yang; Peng, Zining; Pang, Liping; Li, Junyan; Xiao, Jun‐An; Zhang, Yuanfei; Cui, Jianguo

doi:10.1016/j.steroids.2023.109217

Cited by 5 publications

(9 citation statements)

References 35 publications

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“…Compounds such as methylseleninic acid [ 17 ], methylselenocysteine [ 18 , 19 ], and selenomethionine [ 20 , 21 ] have been extensively studied, and their anticancer activity in vitro has been demonstrated. Other functional groups with Se are continuously being reported as cytotoxic for cancerous cell lines, including selenocyanates [ 22 , 23 ], selenoesters [ 24 , 25 ], selenides and diselenides [ 26 , 27 ], selenoureas [ 28 , 29 , 30 ], isoselenocyanates [ 31 , 32 ], and heterocyclic selenazo compounds [ 33 , 34 ] among others [ 35 , 36 , 37 , 38 , 39 ]. The unique properties of this element contained in molecules have emerged as a promising line of research.…”

Section: Introductionmentioning

confidence: 99%

Seleno-Warfare against Cancer: Decoding Antitumor Activity of Novel Acylselenoureas and Se-Acylisoselenoureas

Angulo-Elizari,

Raza,

Encío

et al. 2024

Pharmaceutics

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Currently, cancer remains a global health problem. Despite the existence of several treatments, including chemotherapy, immunotherapy, and radiation therapy, the survival rate for most cancer patients, particularly those with metastasis, remains unsatisfactory. Thus, there is a continuous need to develop novel, effective therapies. In this work, 22 novel molecules containing selenium are reported, including seven Se-acylisoselenoureas synthesized from aliphatic carbodiimides as well as acylselenoureas with the same carbo- and heterocycles and aliphatic amines. After an initial screening at two doses (50 and 10 µM) in MDA-MB-231 (breast), HTB-54 (lung), DU-145 (prostate), and HCT-116 (colon) tumor cell lines, the ten most active compounds were identified. Additionally, these ten hits were also submitted to the DTP program of the NCI to study their cytotoxicity in a panel of 60 cancer cell lines. Compound 4 was identified as the most potent antiproliferative compound. The results obtained showed that compound 4 presented IC50 values lower than 10 µM in the cancer cell lines, although it was not the most selective one. Furthermore, compound 4 was found to inhibit cell growth and cause cell death by inducing apoptosis partially via ROS production. Overall, our results suggest that compound 4 could be a potential chemotherapeutic drug for different types of cancer.

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Section: Introductionmentioning

confidence: 99%

Seleno-Warfare against Cancer: Decoding Antitumor Activity of Novel Acylselenoureas and Se-Acylisoselenoureas

Angulo-Elizari,

Raza,

Encío

et al. 2024

Pharmaceutics

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“…The efficacy of selenocompounds as anticancer agents is correlated with their metabolic route, dose, and the chemical form of Se [ 5 , 18 ]. Hence, the main Se entities that have been widely explored to date are selenides [ 19 , 20 , 21 , 22 ], selenocyanates [ 22 , 23 , 24 , 25 , 26 ], isoselenocyanates [ 27 , 28 , 29 ], selenazo heterocyclic compounds [ 13 , 30 , 31 ], selenoesters [ 32 , 33 , 34 ], selenoureas [ 35 , 36 , 37 , 38 , 39 ], and diselenides [ 19 , 22 , 23 , 24 , 25 , 39 , 40 ]. Additionally, several compounds bearing these functionalities have also been reported to have a potent radical scavenging capacity, allowing the design of molecules with an interesting dual profile as antioxidant and antiproliferative agents [ 19 , 25 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

First Generation of Antioxidant Precursors for Bioisosteric Se-NSAIDs: Design, Synthesis, and In Vitro and In Vivo Anticancer Evaluation

Ramos-Inza,

Aliaga,

Encío

et al. 2023

Antioxidants

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The introduction of selenium (Se) into organic scaffolds has been demonstrated to be a promising framework in the field of medicinal chemistry. A novel design of nonsteroidal anti-inflammatory drug (NSAID) derivatives based on a bioisosteric replacement via the incorporation of Se as diacyl diselenide is reported. The antioxidant activity was assessed using the DPPH radical scavenging assay. The new Se-NSAID derivatives bearing this unique combination showed antioxidant activity in a time- and dose-dependent manner, and also displayed different antiproliferative profiles in a panel of eight cancer cell lines as determined by the MTT assay. Ibuprofen derivative 5 was not only the most antioxidant agent, but also selectively induced toxicity in all the cancer cell lines tested (IC50 < 10 µM) while sparing nonmalignant cells, and induced apoptosis partially without enhancing the caspase 3/7 activity. Furthermore, NSAID derivative 5 significantly suppressed tumor growth in a subcutaneous colon cancer xenograft mouse model (10 mg/kg, TGI = 72%, and T/C = 38%) without exhibiting any apparent toxicity. To our knowledge, this work constitutes the first report on in vitro and in vivo anticancer activity of an unprecedented Se-NSAID hybrid derivative and its rational use for developing precursors for bioisosteric selenocompounds with appealing therapeutic applications.

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“…During the recent decades, much information about methods of SeSt synthesis has appeared [1]. Recently, selenocyano groups were directly introduced into pregnenolone, estradiol, and estrone [5] as well as using cholesterol and norcholesterol [6]. The results of that research indicate that some of the obtained SeSt exhibit antiproliferative properties against cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…So far, little research has focused on the effects of SeSt on cells, and most studies have been limited to determining the effect of these compounds on the rate of cell proliferation with the determination of GI50 (growth inhibition-concentration of the compound resulting in a 50% reduction in the number of cells) or IC50 (inhibition concentration-concentration of compound causing 50% of metabolism inhibition) values in various in vitro tumor models [3,4,7,8] and bacteria [9]. Recent publications have also documented the inhibitory effects of selenosteroids on human tumors in animal models [5,6,10]. There is also information about the antioxidant actions of some SeSt [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Answers to these questions may guide further syntheses to optimize anti-proliferative effects. Knowing the previous data on the antiproliferative effect of SeSt on cells [1,[4][5][6]10], we assumed that the tested compounds may have pro-apoptotic properties. From the point of view of their medical use, it is important which apoptotic pathway is activated [12].…”

Section: Introductionmentioning

confidence: 99%

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New Steroidal Selenides as Proapoptotic Factors

Jastrzebska,

Wawrusiewicz-Kurylonek,

Grześ

et al. 2023

Molecules

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Cytostatic and pro-apoptotic effects of selenium steroid derivatives against HeLa cells were determined. The highest cytostatic activity was shown by derivative 4 (GI50 25.0 µM, almost complete growth inhibition after three days of culture, and over 97% of apoptotic and dead cells at 200 µM). The results of our study (cell number measurements, apoptosis profile, relative expression of apoptosis-related APAF1, BID, and mevalonate pathway-involved HMGCR, SQLE, CYP51A1, and PDHB genes, and computational chemistry data) support the hypothesis that tested selenosteroids induce the extrinsic pathway of apoptosis by affecting the cell membrane as cholesterol antimetabolites. An additional mechanism of action is possible through a direct action of derivative 4 to inhibit PDHB expression in a way similar to steroid hormones.

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Synthesis and antitumor activity of some cholesterol-based selenocyanate compounds

Cited by 5 publications

References 35 publications

Seleno-Warfare against Cancer: Decoding Antitumor Activity of Novel Acylselenoureas and Se-Acylisoselenoureas

Seleno-Warfare against Cancer: Decoding Antitumor Activity of Novel Acylselenoureas and Se-Acylisoselenoureas

First Generation of Antioxidant Precursors for Bioisosteric Se-NSAIDs: Design, Synthesis, and In Vitro and In Vivo Anticancer Evaluation

New Steroidal Selenides as Proapoptotic Factors

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