Novel seleno- and thio-urea derivatives with potent in vitro activities against several cancer cell lines

Alcolea, Verónica; Plano, Daniel; Karelia, Deepkamal; Palop, Juan Antonio; Amin, Shantu; Sanmartín, Carmen; Sharma, Arun

doi:10.1016/j.ejmech.2016.02.042

Cited by 48 publications

(37 citation statements)

References 43 publications

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“…The final compound was purified taking advantage of its solubility properties. The synthesis of the remaining 34 derivatives has been previously published by our group [ 28 , 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…For the remaining compounds of series 1 , 2 , 3 , 4 , 5 and 6 , cytotoxic activity had already been evaluated following the same methodology [ 28 ]. Cell viability assays for compounds of series 7 and 8 had already been screened in a panel of six human cancer cell lines: 1205Lu (melanoma), A549 (lung), DU145 (prostate), HCT116 (colon), PANC-1 (pancreas) and BxPC3 (pancreas) [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…Chemicals were purchased from E. Merck (Darmstadt, Germany), Panreac Química S.A. (Barcelona, Spain), Sigma-Aldrich Quimica, S.A. (Madrid, Spain) and Acros Organics (Janssen Pharmaceuticalaan, Geel, Belgium). The synthesis of 34 out of the 40 compounds analysed in this work has been previously described [ 28 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

“…Those heteroaryl derivatives that exhibited promising cytotoxic activity (VA7J, VA6O and VA5P) in previous publications from the group [ 28 , 29 ] have the potential to continue the drug discovery process. With the objective of predicting the non-desired transitions or degradation processes that may occur along with the already mentioned pharmaceutical manufacturing processing, we proceeded to the thermal characterization and preliminary stability studies of the leader compounds.…”

Section: Introductionmentioning

confidence: 99%

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Antitumoural Sulphur and Selenium Heteroaryl Compounds: Thermal Characterization and Stability Evaluation

et al. 2017

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The physicochemical properties of a compound play a crucial role in the cancer development process. In this context, polymorphism can become an important obstacle for the pharmaceutical industry because it frequently leads to the loss of therapeutic effectiveness of some drugs. Stability under manufacturing conditions is also critical to ensure no undesired degradations or transformations occur. In this study, the thermal behaviour of 40 derivatives of a series of sulphur and selenium heteroaryl compounds with potential antitumoural activity were studied. In addition, the most promising cytotoxic derivatives were analysed by a combination of differential scanning calorimetry, X-ray diffraction and thermogravimetric techniques in order to investigate their polymorphism and thermal stability. Moreover, stability under acid, alkaline and oxidative media was tested. Degradation under stress conditions as well as the presence of polymorphism was found for the compounds VA6E and VA7J, which might present a hurdle to carrying on with formulation. On the contrary, these obstacles were not found for derivative VA4J.

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“…The final compound was purified taking advantage of its solubility properties. The synthesis of the remaining 34 derivatives has been previously published by our group [ 28 , 29 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antitumoural Sulphur and Selenium Heteroaryl Compounds: Thermal Characterization and Stability Evaluation

et al. 2017

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“…Taking into account all these considerations, it is clear that the activity of Se is dependent on the specific constructs in which it is incorporated, and the failure of some Se compounds should not be generalized to all Se derivatives. Recently, our group and many others have demonstrated that the incorporation of Se into organic frameworks, in particular small molecules such as selenocyanate, diselenide, selenourea or selenide, confers unique and very valuable properties against a range of diseases 14,15 , and demonstrate anticancer activity against different cancer types 16,17,18 . Among these small Se-containing mole-cules, Se heterocycles have demonstrated low toxicity for healthy cells, along with promising anticancer effects.…”

Section: Introductionmentioning

confidence: 99%

Activity enhancement of selective antitumoral selenodiazoles formulated with poloxamine micelles

Úriz

Sanmartín

Plano

et al. 2018

Colloids and Surfaces B: Biointerfaces

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Selenium (Se) incorporated into organic frameworks has demonstrated anticancer activity against several cancer types. One of the drawbacks of most of these constructs is their poor solubility and bioavailability, which can be overcome with the use of suitable nanocarriers. We have synthesized a series of 5-substituted amide selenodiazoles, based on the parent structure of ebselen, an organoselenium drug with proven cytoprotective activity, and solubilized them in polymeric micelles of poloxamines, poly(ethylene oxide)-poly(propylene oxide) X-shaped tetrablock-copolymers. Scattering methods (SANS and DLS) were employed to characterize the micellar nanocarriers. MTT biological evaluation highlights the selectivity of the Se-compounds towards cancer cells, with MCF-7 standing as the most responsive line. The alkylation of the heterocycle with a 12-carbon hydrophobic tail displays the highest activity, showing a 100-fold increase with respect to ebselen. This compound also exhibits the greatest increase in solubility in poloxamine micelles, overall resulting in a one-fold increase in activity with respect to the non-formulated form, making it a hit compound for further optimization.

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The Search for Histamine H₄ Receptor Ligands with Anticancer Activity among Novel (Thio)urea Derivatives

et al. 2019

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A series of 33 novel (thio)urea-containing compounds were initially designed and synthesized as potential ligands for the histamine H 4 receptor (H 4 R). However, only 3 compounds showed a statistically significant affinity towards H 4 R (K i < 10 μM). Considering the structural analogy of these thioureas to previously described seleno/thiourea compounds with anticancer and/or reversal multidrug resistance action in cancer cells, selected thioureas were evaluated in in vitro cytotoxicityand cancer multidrug resistance assays. The thiourea derivatives showed a good cytotoxic activity, being the compound 13 d (4-methyl-N-(p-phenylphenyl)-piperazine-1-carbothiamide) the most active (IC 50 = 11.9 μM). They also enhanced the cytotoxicity of the topoisomerase inhibitors topotecan and doxorubicin in a checkerboard combination assay. Compound 13 d showed the strongest synergistic effect on topotecan activity, whereas 13 c (4-methyl-N-(p-tolyl)-piperazine-1-carbothiamide) was the best in combination with doxorubicin. These results can be a good starting point to design more potent and effective (thio)urea derivatives with anticancer activity.[a] Dr.

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Novel seleno- and thio-urea derivatives with potent in vitro activities against several cancer cell lines

Cited by 48 publications

References 43 publications

Antitumoural Sulphur and Selenium Heteroaryl Compounds: Thermal Characterization and Stability Evaluation

Antitumoural Sulphur and Selenium Heteroaryl Compounds: Thermal Characterization and Stability Evaluation

Activity enhancement of selective antitumoral selenodiazoles formulated with poloxamine micelles

The Search for Histamine H₄ Receptor Ligands with Anticancer Activity among Novel (Thio)urea Derivatives

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Novel seleno- and thio-urea derivatives with potent in vitro activities against several cancer cell lines

Cited by 48 publications

References 43 publications

Antitumoural Sulphur and Selenium Heteroaryl Compounds: Thermal Characterization and Stability Evaluation

Antitumoural Sulphur and Selenium Heteroaryl Compounds: Thermal Characterization and Stability Evaluation

Activity enhancement of selective antitumoral selenodiazoles formulated with poloxamine micelles

The Search for Histamine H4 Receptor Ligands with Anticancer Activity among Novel (Thio)urea Derivatives

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The Search for Histamine H₄ Receptor Ligands with Anticancer Activity among Novel (Thio)urea Derivatives