Selenocoumarins as new multitarget antiproliferative agents: Synthesis, biological evaluation and in silico calculations

Lagunes, Irene; Begines, Paloma; Silva, Adrián M.T.; Galán, Alexis R.; Puerta, Adrián; Fernandes, Miguel X.; Maya, Inés; Fernandez‐Bolanos, J.; López, Óscar; Padrón, José M.

doi:10.1016/j.ejmech.2019.06.073

Cited by 27 publications

(14 citation statements)

References 45 publications

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“…For antiproliferative assays, the median and standard deviation (SD) for 2-3 measurements were calculated. (19) To a solution of 3-bromopropanoic acid (100.0 mg, 0.65 mmol) in anhydrous DMF (6 mL) was added potassium selenocyanate (376.7 mg, 2.61 mmol, 4.0 equiv.). The corresponding mixture was stirred overnight at 60 • C, under inert atmosphere (Ar) and in the dark.…”

Section: Discussionmentioning

confidence: 99%

“…Organoselenium motifs have been combined with many other pharmacophores, like phenolic compounds [13,14], iminosugars [15], steroids [16,17], non-steroidal anti-inflammatory drugs [18], heterocycles [19][20][21], nucleosides [22], quinones [23], or metal coordination complexes [24] among others, or incorporated into the structures of natural products, like carbohydrates, giving access to the so called selenosugars [25]. The combination of chitosan and selenium nanoparticles has recently been reported as a vector for the transportation of mRNA for amplifying immune response in the potential development of cancer vaccines [26].…”

Section: Introductionmentioning

confidence: 99%

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Masked Phenolic-Selenium Conjugates: Potent and Selective Antiproliferative Agents Overcoming P-gp Resistance

et al. 2020

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Cancer accounts for one of the most complex diseases nowadays due to its multifactorial nature. Despite the vast number of cytotoxic agents developed so far, good therapeutic approaches are not always reached. In recent years, multitarget drugs are gaining great attention against multifactorial diseases in contraposition to polypharmacy. Herein we have accomplished the conjugation of phenolic derivatives with an ample number of organochalcogen motifs with the aim of developing novel antiproliferative agents. Their antioxidant, and antiproliferative properties (against six tumour and one non-tumour cell lines) were analysed. Moreover, in order to predict P-gp-mediated chemoresistance, the P-glycoprotein assay was also conducted in order to determine whether compounds prepared herein could behave as substrates of that glycoprotein. Selenium derivatives were found to be significantly stronger antiproliferative agents than their sulfur isosters. Moreover, the length and the nature of the tether, together with the nature of the organoselenium scaffold were also found to be crucial features in the observed bioactivities. The lead compound, bearing a methylenedioxyphenyl moiety, and a diselenide functionality, showed a good activity (GI50 = 0.88‒2.0 µM) and selectivity towards tumour cell lines (selectivity index: 14‒32); moreover, compounds considered herein were not substrates for the P-gp efflux pump, thus avoiding the development of chemoresistance coming from such mechanism, commonly found for widely-used chemotherapeutic agents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Masked Phenolic-Selenium Conjugates: Potent and Selective Antiproliferative Agents Overcoming P-gp Resistance

et al. 2020

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“…Owing to the fact that a number of synthetic organoselenium compounds have been synthesized for their use as redox-modulators in the last few years [40][41][42], the antioxidant activity of the selected synthesized compounds are further estimated employing different biochemical assays such as DPPH, bleomycin-dependent DNA damage and Gpx-like assays [43,44].…”

Section: Antioxidant Assaymentioning

confidence: 99%

Synthesis and biological evaluation of organoselenium (NSAIDs-SeCN and SeCF3) derivatives as potential anticancer agents

Zhong

et al. 2020

European Journal of Medicinal Chemistry

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A series of organoselenium compounds based on the hybridization of nonsteroidal antiinflammatory drugs (NSAIDs) scaffolds and Se functionalities (-SeCN and -SeCF 3 ) were synthesized and characterized, and evaluated against four types of cancer cell lines, SW480 (human colon adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells), MCF-7 (human breast adenocarcinoma cells). Interestingly, most of the investigated compounds showed active in reducing the viability of different cancer cell lines. The most active compound 3h showed IC 50 values lower than 20 μM against the four cancer cell lines, particularly to SW480 and MCF-7 with IC 50 values of 4.9 and 3.4 μM, respectively. Furthermore, NSAIDs-SeCN derivatives (2h and 2i) and NSAIDs-SeCF 3 derivatives (3h and 3i) were selected to investigate their ability to induce apoptosis in MCF-7 cells via modulation the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic caspase-3 protein. Moreover, the redox properties of the synthesized organoselenium candidates were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Taken together, these NSAIDs-Se candidates could provide promising new lead derivatives for further potential anticancer drug development.

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“…Several organoselenium agents have been developed for the inhibition of different types of cancer cell growth. Among them, selenoureas represent a group of simple but well-studied molecules with anticancer and/or antioxidant properties [ 15 , 16 , 17 , 18 , 19 , 20 ]. In addition, our research team has reported the preparation and cytotoxic and antioxidant activities for different selenourea derivatives [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Novel N,N′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents

et al. 2021

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A series of 30 novel N,N disubstituted selenoureas were synthesized, characterized, and their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cytotoxic activity was tested in vitro in a panel of three different cancer (breast, lung and colon) and two normal cell lines. Each selenourea entity contains a para-substituted phenyl ring with different electron-withdrawing and electron-donating groups, and different aliphatic and aromatic nuclei. All of the synthesized selenoureas present antioxidant capacity at high concentrations in the DPPH assay, and three of them (2b, 2c and 2d) showed greater radical scavenging capacity than ascorbic acid at lower concentrations. These results were confirmed by the ABTS assay, where these novel selenoureas present even higher antioxidant capacity than the reference compound Trolox. On the other hand, 10 selenoureas present IC50 values below 10 µM in at least one cancer cell line, resulting in the adamantyl nucleus (6a–6e), the most interesting in terms of activity and selectivity. Outstanding results were found for selenourea 6c, tested in the NCI60 cell line panel and showing an average GI50 of 1.49 µM for the 60 cell lines, and LC50 values ranging from 9.33 µM to 4.27 µM against 10 of these cancer cell lines. To gain insight into its anticancer activity mechanism, we investigated the cell cycle progression of the promising compound 6c, as well as the type of programmed-cell death in a colon cancer cell line it provokes (HT-29). Compound 6c provoked S phase cell cycle arrest and the induction of cell death was independent of caspase activation, suggesting autophagy, though this assertion requires additional studies. Overall, we envision that this compound can be further developed for the potential treatment of colon cancer.

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Selenocoumarins as new multitarget antiproliferative agents: Synthesis, biological evaluation and in silico calculations

Cited by 27 publications

References 45 publications

Masked Phenolic-Selenium Conjugates: Potent and Selective Antiproliferative Agents Overcoming P-gp Resistance

Masked Phenolic-Selenium Conjugates: Potent and Selective Antiproliferative Agents Overcoming P-gp Resistance

Synthesis and biological evaluation of organoselenium (NSAIDs-SeCN and SeCF3) derivatives as potential anticancer agents

Novel N,N′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents

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